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- Using a crack team of doctors and his wits, an antisocial maverick doctor specializing in diagnostic medicine does whatever it takes to solve puzzling cases that come his way.
- Two New Yorkers accused of murder in rural Alabama while on their way back to college call in the help of one of their cousins, a loudmouth lawyer with no trial experience.
- Take two rival television reporters: one handsome, one talented, both male. Add one producer, female. Mix well, and watch the sparks fly.
- A mute gunfighter defends a young widow and a group of outlaws against a gang of bounty killers in the winter of 1898, and a grim, tense struggle unfolds.
- An eccentric Scottish schoolteacher's extravagantly romantic ideas about life--and love--overly impress her young pupils and bring her into conflict with her school's conservative headmistress.
- In 1876 Colorado, the Tomahawk and Western Railroad is expanding through the Rockies but some stagecoach operators, fearing a loss of revenue, plan to sabotage the railroad.
- Young farmboy who always wanted to be a cowhand talks a tough trail boss into hiring him on a cattle drive.
- The Halsworths' nearly-final divorce suddenly gets complicated when Miriam's old flame comes to town.
- House treats a patient on death row while Dr. Cameron avoids telling a patient she has a terminal illness.
- While House and his team scramble to discover what's causing brain and kidney dysfunction in a pregnant woman, Vogler is on the warpath to get House fired.
- The team takes care of a student with inexplicable electrical shocks, and House's parents visit.
- A nun suffering from acute dermatitis and asthma treated by House with possibly the wrong medication comes dangerously close to death.
- When a famous writer is brought in with language difficulties, House must assist via phone while waiting for a delayed plane.
- A woman comes down with symptoms of African sleeping sickness, but there seems to be no way she could have contracted it. House and his aides must ask a few tough questions and make some tough decisions in order to try to save her.
- A patient with 40% body burns and inexplicable cardiac and neurological signs is treated by the team, while House pursues disproving an old enemy's medical study.
- A morbidly obese ten-year-old girl has a heart attack, and her mother insists that House and his team look past her weight to find the diagnosis. Meanwhile, Vogler pressures House to fire a member of his staff. Clinic Patients: Unidentified man with an infected pierced scrotum; overweight woman with a 30-pound tumor on her ovaries who refuses to have it removed, because she worries she will be unattractive.
- Cuddy joins the team after her handyman falls off of her roof and begins to develop bizarre symptoms. Clinic Cases: African American man who objects to "minority meds."