We evaluated the efficacy, tolerability, and safety of olanzapine monotherapy in 20 adult patients with bipolar I or II disorder, depressed phase. Patients received open-label olanzapine monotherapy (mean modal dose, 15 mg/day) for 8 weeks. Assessments of psychopathology (Montgomery-Asberg Depression Rating Scale [MADRS], Quick Inventory of Depressive Symptomatology [QIDS-SR-16], Young Mania Rating Scale [YMRS]), clinical global state (Clinical Global Impressions [CGI] scale), and safety/tolerability were performed at baseline, and at 1, 2, 4, 6, and 8 weeks. Seventeen patients (85.0%) completed the study. Improvement in MADRS total scores was observed after the first week of treatment, and at all remaining follow-up time points ( p≤0.005). Parallel improvement in QIDS-SR-16 (p<0.001) and CGI-Severity (p<0.001) was observed between baseline and study endpoint. Nine (45%) subjects achieved positive treatment response, eight of whom (40%) also achieved symptom remission. There were significant increases in weight (+3.2 kg, p=0.001) and body mass index (+1.1 kg/m2, p=0.001), but not fasting glucose or lipids, with the exception of reduced triglyceride levels in the overall sample, and reduced HDL cholesterol in females. Olanzapine may be an effective, well-tolerated option for treating acute non-psychotic depression across a variety of bipolar disorder subtypes. Copyright © 2009 John Wiley & Sons, Ltd.