It is hundreds of years after the events of
Alien³. Doctors aboard a space station called the
Auriga are working on a secret project for the military; they have been attempting to produce a clone of Ellen Ripley (
Sigourney Weaver) working from a blood sample that was collected from Fiornia 61, the planet where she died. In doing so, they hope that they can harvest the alien embryo that was gestating inside of her at the time. Dr. Wren (
J.E. Freeman) and his team of colleagues have succeeded with their eighth attempt. They operate on the Ripley clone and remove the embryonic alien queen, which is still too small to struggle with the robotic arms used for the operation. After the alien is removed, Dr. Wren and his colleague, Dr. Gediman (
Brad Dourif), decide to keep the clone alive for further study. They repair the wound in her chest.
The Ripley clone begins to gain consciousness at an unprecedented rate. The ship's doctors go through exercises with her regarding language and learning, and she responds positively. She also exhibits a frightening predatory physical power, able to break her bonds and attack at will. The doctors and orderlies are only barely able to subdue her. She seems to share DNA with the alien creatures, explaining her unusual strength, and her blood is also slightly acidic. The experiment angers General Perez (
Dan Hedaya), the military figure in charge of the operation. He is only interested in the alien queen, which has also grown at a terrifying rate; it is now almost full size and is contained within a super strong cell on the ship.
The Ripley clone seems to sense what is going on. One day she eats with Gediman and Wren, and she reveals a startling flash of her former self; it seems as if the clone has retained some of Ripley's memories and personality traits. It is almost as if the woman herself has been recreated and is slowly awakening. Ripley has a fragmented conversation with Wren. "How did you...?" she asks. Wren tells her how they painstaking recreated her, and she intuitively guesses that they wanted the alien. Even in her dazed condition, she is cynical and tells them that they can't control it.
Enter the
Betty, a ragtag ship carrying a crew of space pirates. Their cargo is the crew of another ship, still in their cryogenic containers and asleep, unaware that they have been hijacked. General Perez has hired the crew, led by Elgyn (
Michael Wincott), to deliver the unfortunate sleeping space travelers to be used as breeding for aliens. Before long the kidnapped people have been impregnated with aliens, and a number of drone aliens are now in containment units on board the ship.
The
Betty crew find Ripley exercising in a rec center, tossing a basketball around. Johner (
Ron Perlman), a brutish and odd looking man, attempts to engage her in a predatory manner of flirting with her, but Ripley easily out-maneuvers him and proves herself to be physically powerful beyond his expectations.
One of the
Betty's crew, a young waifish girl named Call (
Winona Ryder), seems to have a different agenda. She slips away from the others and finds Ripley's containment unit, gaining illegal access to it. There she finds Ripley and wakes her up; Call admits that she came here to kill Ripley, but Ripley is far too cunning to allow that. She even deliberately presses her hand onto Call's knife, and the resulting wound heals itself rapidly. Call can tell that the doctors have removed the alien embryo already, and she tells Ripley that she is just a clone, something the doctors consider only a byproduct. Ripley seems confused and hurt by this, but she knows it is true. She releases Call, who goes outside the cell only to be intercepted by guards.
Gediman is furious about Call's trespassing, and he attempts to execute the crew of the
Betty as terrorists. A number of things happen simultaneously. The
Betty crew has a standoff with soldiers who have orders to execute them. Wren, who is experimenting with adult aliens in a cell, inadvertently teaches them how to use the equipment. Together the aliens revolt; two of them gang up on a third and kill it, causing its acid blood to eat through the floor of the containment unit. Suddenly the aliens are out, and they quickly begin to take over the ship. Ripley, whom General Perez has ordered to be executed, escapes from her cell before the soldiers can carry out their orders. The ship goes into emergency mode and some people escape in life pods; the unfortunate ones are killed by aliens. The crew of the
Betty bands together, but Elgyn is killed by the creatures. Ripley joins Call and the others as they make their way across the
Auriga to the bay where the
Betty is docked. They take Gediman with them, although he is more of a hostage.
Along the way they find the laboratory where Gediman and the others created the Ripley clones; inside are the previous seven attempts, all of them hideously deformed and bizarre human/alien hybrids. Six are dead and contained in stasis tubes, but the seventh attempt is the most heartbreaking; she is human enough to be identifiable, yet her limbs and her body are misshapen and alien. Even worse, she is still living, kept alive by tubes and ventilators. Ripley 8 is horrified, realizing now exactly what she is and where she came from. Ripley 7 begs her to kill her, and Ripley 8 uses grenades and a flamethrower to destroy the other clones. Gediman is morbidly amused by her inner turmoil over her bizarre identity, and Ripley 8 looks at him in utter rage and disgust. Johner has no idea what caused Ripley's rampage; "Must be a chick thing!" he quips.
Another strange discovery: the room containing what's left of the hijacked crew that the
Betty crew delivered to General Perez. One of the crew members, Larry Purvis (
Leland Orser), is still alive, but Ripley suggests they leave him behind. She can sense that he is gestating an alien embryo, having been impregnated by a facehugger. Call insists that they bring him along, that perhaps if they make it to the
Betty in time, they can perform some kind of surgery to save his life.
A hitch in their escape plan occurs when they find that they are forced to traverse the mess hall; unfortunately, it is completely underwater now due to a flood that occurred during the chaos of the alien escape. Everyone must hold their breath for a painful amount of time, and Hillard from the
Betty is snatched along the way by aliens that emerge, swimming after her. Ripley watches, strangely fascinated by the creatures.
When they emerge on the other side of the tunnel, they find that they've been ambushed; the shaft leading upwards from the mess hall has been festooned with alien eggs, which eject facehuggers at the humans. Ripley gets one on her face, but her inhuman strength allows her to easily rip it away from herself, a strange twist on the similar incident that happened to her in
Aliens. A grenade clears the shaft of eggs and allows the crew to climb the ladder to the top, but aliens emerge from the water below them and attack. Christie (
Gary Dourdan), a
Betty pirate, is killed, and when Call and Gediman reach the top of the shaft first, Gediman talks her into giving him her gun and shoots her in the chest; her body falls back down into the water and drifts away. Ripley is horrified, as she has found something strangely compelling about Call. Gediman escapes the shaft and seals everyone else inside of it, but the door eventually opens again from the other side; Call has somehow survived the gunshot and rescued them.
Ripley is not fooled, as she knows she saw Call get shot in the chest at point blank range. She makes Call show everyone the wound, revealing wires and white android blood. Call confesses that she is one of a legendary model of androids who were so lifelike that they gained consciousness and rebelled, burning their internal wireless modems and trying to pass as human. The soldier Distephano (
Raymond Cruz) who is with them is geeked about actually seeing this kind of android; Call seems humiliated that her secret has been discovered. Ripley now understands why she feels a kinship with Call; both of them are somehow artificial, creatures that have been created in the likeness of human beings but who are distinctively different. Call reveals that before she burned her modem, she accessed the mainframe and discovered the plans that General Perez had for cultivating the aliens by cloning Ripley. Her personal mission was to destroy the operation and keep this from happening, as she understands that the aliens will wipe out humankind.
Knowing Call's capabilities, Ripley takes her to a small chapel, where they find a computer interface. Although Call does not want to make use of her android functions, Ripley urges her to take over the
Auriga's computer. Call discovers that the
Auriga went into emergency mode after the attack; it is now automatically returning to Earth, where surely the aliens will escape and infect the human race. Ripley instructs Call to crash the ship in any way possible. Call blocks Gediman from reaching the
Betty and makes a sarcastic page summoning all aliens to the deck where he is.
When they set out for the
Betty again, Ripley is snatched through the floor grating by aliens. Her connection to the creatures comes full circles; they recognize her as one of their own and take her to the nest, which is crawling with aliens and which also contains the queen. Wren is there, too, coccooned and delirious, and he tells Ripley that the queen inherited Ripley's reproductive cycle. After laying her first round of eggs, she gives birth as a human being would, birthing a bizarre creature that resembles a human being crossed with an alien. The Newborn kills the queen and embraces Ripley as its mother. It attacks Wren, biting off the top of his head. Ripley escapes the nest and races to rejoin the others as the
Betty takes off. She makes it just in time, and the others are fortunate that she does; with their pilots dead, Ripley seems to be the only one of them who has the experience to fly the ship. "Are you kidding," she tells them, "This piece of shit's older than I am."
There is final confrontation when Call goes to close the storage bay lock and discovers the Newborn has stowed away. She barely manages to evade it. Distephano comes into the bay and is killed. Ripley senses that something is wrong and comes back to find the Newborn cornering Call. She distracts it by speaking soothingly to it; it trusts Ripley as it thinks she is its mother. She deliberately cuts her hand on its sharp teeth and flicks the acidic blood onto the glass porthole. Her blood dissolves a hole in the glass, depressurizing the cabin and sucking the Newborn onto the window. It hovers there pitifully as it is slowly sucked out through the tiny hole; Ripley feels torn between her desire to exterminate the species and the loyalty she feels toward them since she has their DNA. She watches in horror as the Newborn is slowly destroyed, aware that it is dying.
The
Betty breaches Earth's atmosphere safely and Ripley and Call look out the porthole at the clouds and the sun, dazed by their experience and wondering what the future will hold for both of them. Neither one has ever been to Earth before.