OBJECTIVE: The characteristics of patients who cycle from mania to major depression and the frequencies of these cycles remain poorly understood. METHOD: This study compared 28 patients with a first episode of mania who cycled into a major depressive episode without recovery from their index episode and 148 patients with first-episode mania who did not cycle into depression. Patients were given extensive assessments at baseline and 6-, 12-, and 24-month follow-ups. Comparisons between the two groups were made on demographic variables, clinical ratings, and outcome variables. RESULTS: Approximately 16% of the patients with a first episode of mania cycled into major depression. Patients who cycled into depression were more likely to have higher depressive scores at admission and tended to have the mixed subtype of bipolar disorder. CONCLUSIONS: Patients with first-episode mania who score high for depression at admission may be at greater risk of cycling into a major depressive episode.