In Missouri, the forensic psychiatrist Cara Jessup rejects the theory of dissociated or multiple personalities and the prisoner of the death row Joseph Kinkirk has no remission from the governor and is sent to lethal injection. Cara is a widow that raises her daughter Sammy with the support of her brother, Stephen Harding, and Catholic that believes in God. Her father, Dr. Harding, invites Cara to interview the patient David Bernburg, who is a sweet man. Out of the blue, David impersonates the aggressive personality of Adam Saber. Cara is intrigued with the mystery and visits David's mother Mrs. Bernburg (Frances Conroy), who tells her that David had passed away a long time ago. Cara invites Mrs. Bernburg to visit Sam in the hospital and they are surprised with the knowledge of the patient about David's private life. When Sam shifts his personality to Wesley, Cara decides to go further in her investigation and sooner she learns that each personality is actually a dead person...

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In a world ravaged by a virus infection, turning its victims into the Undead, Alice (Jovovich), continues on her journey to find survivors and lead them to safety. Her deadly battle with the Umbrella Corporation reaches new heights, but Alice gets some unexpected help from an old friend. A new lead that promises a safe haven from the Undead takes them to Los Angeles, but when they arrive the city is overrun by thousands of Undead - and Alice and her comrades are about to step into a deadly trap.