The advent of widespread terrorism requires careful attention to preventing multiple cases of post-traumatic stress disorder (PTSD). Controlled studies suggest that early psychological interventions can prevent PTSD in selected groups of survivors. The effectiveness of early interventions in large groups of survivors is unknown. The effect of pharmacological prevention is equally unknown. The proposed work will test the hypothesis that cognitive behavioral therapy (CBT) and, independently, sertraline will effectively prevent PTSD when provided, within a month of a traumatic event, to highly distressed survivors, who are systematically identified in a large cohort of trauma-exposed individuals. It will also evaluate the extent to which a program to systematically prevent PTSD by early interventions is feasible, acceptable to survivors and effectively reduces morbidity. The proposed work consists of two embedded procedures: a comprehensive outreach and structured telephone evaluation of 4000 survivors, performed one week and seven months following a traumatic event, and an embedded randomized controlled trial of CBT, sertraline, and a wait list, offered within a month of a traumatic event to survivors with symptoms of acute stress disorder. Survivors in the wait list will receive CBT three months later. Repeated clinical assessments will probe treatment efficacy. Repeated telephone evaluations will assess treatment effectiveness. The study will generate vital knowledge about the feasibility and the effectiveness of secondary prevention of PTSD in large cohorts of survivors.