Background: The treatment of bipolar depression is problematic. Mood stabilizing agents are often inadequate, while antidepressants may induce mania or mood destabilization. Methylphenidate has been advocated as an effective antidepressant agent in unipolar depression, and depression secondary to medical illness. Amphetamine administration has been shown to reduce manic behavior. These independent observations suggest that methylphenidate may be a safe and effective agent in bipolar depression. Methods: Fourteen depressed subjects with DSM-IV bipolar illness and a Hamilton-depression (HAM-D) scale score of at least 15 had methylphenidate added to a stable mood stabilizer regiment. Patients were followed weekly for if weeks and then biweekly for an additional 8 weeks. Results: HAM-D scores dropped from 16.9 +/- 1.79 SD at baseline to 9.4 +/- 9.73 on week 12 (p = 0.12, t = 1.84, df = 6) and 9.8 +/- 7.56 on last observation carried forward (LOCF) (p = 0.019, t = 2.8, df = 10). Psychiatric symptom assessment scale (PSAS) scores dropped from 17.9 +/- 5.63 at baseline to 4.8 +/- 7.47 at week 12 (p = 0.016, t = 4.02, df = 4) and 6.3 +/- 6.75 on LOCF (p = 0.007, t = 3.74, df = 7). Three individuals stopped secondary to anxiety, agitation, and hypomania, respectively. Conclusion: In this brief, open study, methylphenidate was effective and relatively safe in depressed bipolar subjects.