To examine the prevalence and correlates of major depression in caregivers of individuals with moderate to severe traumatic brain injuries. Repeated-measures design involving structured diagnostic interview and self-report of psychological distress administered on two occasions separated by 6 months. Three acute care rehabilitation hospitals. Fifty-nine caregivers (39 mothers and 20 spouses) of individuals with moderate to severe brain injuries recruited from previous inpatient rosters. All caregivers were currently residing with the person with traumatic brain injury. The Diagnostic Interview Schedule-Revised [DIS-R] was utilized to assess depression. The Symptom Checklist 90-Revised (SCL 90-R) measured general psychological distress. Forty-seven percent of caregivers initially met diagnostic criteria for depression, and 43% met criteria 6 months later. Nearly two thirds of those who were initially depressed continued to be depressed 6 months later, and 17% of those who were not depressed initially subsequently met criteria for depression. The best predictor of depression was a previous (pre-brain injury) depressive episode. Neither time since injury nor injury severity predicted diagnostic status, and spouses were no more likely to be depressed than were mothers. The SCL 90-R, including its depression scale, showed high specificity but low sensitivity in predicting diagnostic status. The prevalence of major depression is high in caregivers of individuals with brain injuries. Because depression may interfere with the capacity to provide care and contribute to the rehabilitation process, it is important for clinicians to carefully assess both the current and preaccident affective status of primary caregivers.