In the Vatican, Vicar Imani (Djimon Hounsou) shows Cardinal Bruun (Peter Andersson) the case of Angela Holmes (Olivia Taylor Dudley), a young American woman who is suspected of harboring an evil spirit.
Two months earlier in the United States, Angela is given a surprise birthday party by her father, Roger (Dougray Scott), and boyfriend, Peter “Pete” Smith (John Patrick Amedori). She accidentally cuts herself and is rushed to the hospital, where she briefly meets Father Lozano (Michael Peña). She is injected with a serum that causes an infection; at home, she experiences a seizure and is placed under care at a hospital. A few days later, she is released, but in the taxi on the way home, she violently grabs the wheel, causing an accident that puts her in a coma for 40 days. Just as her life support is about to be switched off, she comes round, seemingly in perfect health.
However, Angela begins to show symptoms of demonic possession when she almost drowns a baby, followed by forcing a detective to commit suicide. Lozano sends her to a psychiatric hospital. A distraught Roger confesses that Angela’s mother was a prostitute; she is pregnant just a few months after Roger met her but abandoned the baby at birth leaving Angela to be raised by Roger. Angela’s possession becomes worse; she taunts her psychiatrist, Dr. Richards (Kathleen Robertson), eventually culminating in her speaking in Aramaic that induces hysteria and mass suicide in her fellow patients. Deciding that nothing can save her, the hospital releases her.