We describe two female patients who had severe sulfamethoxazole-trimethoprim-induced thrombocytopenic purpura. One case occurred shortly after initiating therapy, whereas the other began on the seventh day of treatment. Both patients presented a platelet count below 5,000/microL, extensive purpura, and significant vaginal bleeding. Treatment with systemic corticosteroids resulted in rapid resolution of the thrombocytopenia in the first patient, but had no immediate effect in the other. High-dose intravenous immunoglobulin was effective in correcting the thrombocytopenia in this second instance. Both patients were discharged with a tapering 4-week course of oral prednisone and have remained well since.