METHODS Patients with the acquired immunodeficiency syndrome are predisposed to cutaneous drug reactions. The reasons are poorly understood and the circumstances in which such patients can be treated through hypersensitivity are a matter of discussion. We assessed the value of clinical and laboratory parameters for predicting trimethoprim-sulfamethoxazole-induced skin reactions and the effects of continued trimethoprim-sulfamethoxazole therapy in such patients. We retrospectively studied all episodes of nonhypoxemic Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome who were treated with trimethoprim-sulfamethoxazole. RESULTS No clinical or laboratory parameters were found to be predictive of trimethoprim-sulfamethoxazole-induced cutaneous reactions. Of 38 patients treated with trimethoprim-sulfamethoxazole, 18 (47%) developed cutaneous reactions; these occurred within a median of 11 days (range, 7 to 20 days). Of these 18 patients, 12 (67%) continued to be treated with trimethoprim-sulfamethoxazole through hypersensitivity. Trimethoprim-sulfamethoxazole treatment was continued in 19 (95%) of the 20 patients who did not develop cutaneous reactions (P = .067). The mean duration of trimethoprim-sulfamethoxazole therapy was shorter (18 days) in patients who developed skin reactions than in those who did not (20 days) (P = .016). Noncutaneous side effects accounted for all but one interruption of therapy. CONCLUSIONS No clinical or laboratory parameters were found to be predictive of cutaneous reactions. By treating through hypersensitivity, 67% of our patients, who otherwise might have had to stop taking trimethoprim-sulfamethoxazole, were able to continue this essential drug therapy.