The Johns Hopkins Precursors Study, a long-term prospective study, was used to study the relation between self-reported sleep disturbances and subsequent clinical depression and psychiatric distress. A total of 1,053 men provided information on sleep habits during medical school at The Johns Hopkins University (classes of 1948-1964) and have been followed since graduation. During a median follow-up period of 34 years (range 1-45), 101 men developed clinical depression (cumulative incidence at 40 years, 12.2%), including 13 suicides. In Cox proportional hazards analysis adjusted for age at graduation, class year, parental history of clinical depression, coffee drinking, and measures of temperament, the relative risk of clinical depression was greater in those who reported insomnia in medical school (relative risk (RR) 2.0, 95% confidence interval (CI) 1.2-3.3) compared with those who did not and greater in those with difficulty sleeping under stress in medical school (RR 1.8, 95% CI 1.2-2.7) compared with those who did not report difficulty. There were weaker associations for those who reported poor quality of sleep (RR 1.6, 95% CI 0.9-2.9) and sleep duration of 7 hours or less (RR 1.5, 95% CI 0.9-2.3) with development of clinical depression. Similar associations were observed between reports of sleep disturbances in medical school and psychiatric distress assessed in 1988 by the General Health Questionnaire. These findings suggest that insomnia in young men is indicative of a greater risk for subsequent clinical depression and psychiatric distress that persists for at least 30 years.