Trimethoprim-sulfamethoxazole is an important medication for the treatment and prevention of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. Use of this medication has been limited by the high frequency of adverse reactions that occur in patients with human immunodeficiency virus disease. This article reviews the incidence and spectrum of adverse reactions and options for continuing therapy with trimethoprim-sulfamethoxazole in human immunodeficiency virus-infected patients who have adverse reactions.