BACKGROUND Depression has been widely studied in primary care settings, yet studies of medically uninsured populations are lacking. We sought to determine whether depression screening and treatment improved depression scores of a medically uninsured, mostly African American primary care population. METHODS The study was a prospective repeated-measures design that recruited uninsured patients. Patients were screened for depression, and the rate of depression diagnosis was compared with baseline. Patients who were diagnosed and accepted treatment were randomized to 1 of 4 treatment arms: (1) usual care; (2) usual care and psychotherapy; (3) usual care and education and psychotherapy; and (4) usual care and education. Patients were then reevaluated at 8, 12, and 24 weeks. RESULTS A total of 674 patients participated. Depression prevalence was significantly higher among those screened (38%) than at baseline (16%). All treatment groups showed a significant reduction in depression scores over a 6-month period, from a mean score of 15 at baseline to 8.3 at 24 weeks (P < .005). All treatment interventions were equally effective. CONCLUSION Screening improves the rate of diagnosis of depression in an uninsured, primarily African American population, and subsequent treatment significantly reduces the burden of depression.