
At fictional Princeton Plainsboro Teaching Hospital in New Jersey, prickly genius Dr. Gregory House tackles health mysteries as would a medical Sherlock Holmes, all the while playing mind games with colleagues that include his best friend, oncologist James Wilson. House, an acerbic infectious disease specialist, solves medical puzzles with the help of a team of young diagnosticians. Flawless instincts and unconventional thinking help earn House great respect, despite his brutal honesty and antisocial tendencies.

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Still mourning the death of his girlfriend, Wilson resigns from Princeton Plainsboro; House must determine if he is responsible for the death of his best friend's girlfriend; Thirteen struggles to treat a patient objectively.
House and the team investigate a string of deaths centering around a single organ donor; they rush to save the only two surviving recipients; House auditions new best friends and uses a detective to spy on Wilson.
House and the team take on the case of a struggling artist with an undiagnosed illness that's distorting his perception and threatening his career; House continues to have a private investigator dig up dirt on everyone on his team.
After receiving word that his father has passed away, House is coerced into attending the funeral; the team tries to diagnose the illness of a woman who was in China searching for her birth mother.