Co-trimoxazole (trimethoprim-sulfamethoxazole) and pyrimethamine-sulfadoxine have been recommended for treatment and prophylaxis, respectively, of Pneumocystis carinii pneumonia (PCP). However, toxic epidermal necrolysis (TEN) occurred in three of four patients with acquired immunodeficiency syndrome (AIDS) during the course of treatment or prophylaxis of PCP with these agents. On the other hand, 14 patients with PCP treated with pentamidine never developed TEN. Because the incidence of adverse skin reactions is higher among patients with AIDS than those without AIDS, and TEN is a severe, potentially fatal skin reaction, sulfonamide-containing drugs should be given cautiously to patients with AIDS.