OBJECTIVE: The purpose of this study was to measure the longitudinal course of specific symptoms of posttraumatic stress disorder (PTSD) and related symptoms of alcohol and substance abuse and the effects of alcohol and substances on the symptoms of PTSD. METHOD: A structured interview for the assessment of PTSD and alcohol and substance abuse, as well as other factors such as life stressors and treatment, was administered to 61 Vietnam combat veterans with PTSD. RESULTS: Onset of symptoms typically occurred at the time of exposure to combat trauma in Vietnam and increased rapidly during the first few years after the war. Symptoms plateaued within a few years after the war, following which the disorder became chronic and unremitting. Hyperarousal symptoms such as feeling on guard and feeling easily startled developed first, followed by avoidant symptoms and finally by symptoms from the intrusive cluster. The onset of alcohol and substance abuse typically was associated with the onset of symptoms of PTSD, and the increase in use paralleled the increase of symptoms. Patients reported a tendency for alcohol, marijuana, heroin, and benzodiazepines to make PTSD symptoms better, while cocaine made symptoms in the hyperarousal category worse. There was no relationship between treatment interventions and the natural course of PTSD. CONCLUSIONS: These findings suggest that symptoms of PTSD begin soon after exposure to trauma, that hyperarousal symptoms are the first symptoms to occur, that the natural course of alcohol and substance abuse parallels that of PTSD, and that specific substances have specific effects on PTSD symptoms.