Serotonin reuptake inhibitors (SRIs) are now considered the first-line treatment for depression, but they have not been well studied in bipolar disorder. Recently, some authors have recommended that patients at risk for antidepressant-induced mania be treated with SRIs rather than tricyclic antidepressnats (TCAs). Clinical information about 11 patients who developed mania during treatment with SRIs is described. These patients were found to have personal or family histories of hypomania or mania, but these disorders were not usually recognized at the time of the patients' initial treatment for depression. The SRI-induced manic episodes were also quite severe, having psychotic features or requiring patients to be secluded for extreme agitation, but patients responded completely to antimanic treatment. The risk of treatment-emergent mania with SRIs is not trivial, especially among patients at risk for bipolar disorder. Additional research is needed to compare the actual rate of drug-induced mania with SRIs and TCAs in patients with different bipolar subtypes, while controlling for concurrent antimanic drug use. (J Clin Psychopharmacol 1996;16:425-427).