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OBJECTIVE: This study estimated the proportion of patients attending an urban general medical practice with current major depression and a history of bipolar disorder and compared the history, presentation, and treatment of patients with unipolar and bipolar depression. METHOD: A group of 1,143 patients was assessed with measures of past and current mental health and treatment. Patients were partitioned into bipolar and unipolar groups based on a predefined cutoff on the Mood Disorder Questionnaire. The groups were compared on sociodemographic characteristics, depressive symptoms, comorbid mental disorders, and mental health treatment. RESULTS: Approximately one-quarter of the patients with major depression had lifetime bipolar depression. Patients with unipolar and bipolar depression did not significantly differ on background or health characteristics. Patients with bipolar depression were significantly more likely to report hallucinations, current suicidal ideation, and low self-esteem than patients with unipolar depression but less likely to report disturbed appetite. Patients with bipolar depression were significantly more likely to have an alcohol use disorder and to report inpatient psychiatric care and antipsychotic treatment during the past month than patients with unipolar depression. Nearly one-half of the patients with bipolar depression had taken an antidepressant in the last month, but most were not also being treated with an antipsychotic or mood stabilizer. CONCLUSIONS: Bipolar depression is common in urban general medicine practice. When patients took antidepressants, they seldom received concurrent antimanic medications. Because of the risks of treating bipolar disorder with antidepressant monotherapy, physicians should assess their depressed patients for mania before prescribing antidepressants.