Sulfamethoxazole-trimethoprim was administered prophylactically to 786 patients judged to be at sufficient risk for development of Pneumocystis carinii pneumonitis. The selection of patients, administration of the agents, and surveillance for compliance were the responsibility of the attending oncologists rather than specialists in infectious diseases, as in an earlier trial at this center. The recommended dosage was trimethoprim, 150 mg/sq m/day, and sulfamethoxazole, 750 mg/sq m/day. Over a three-year study period, nine cases of P carinii pneumonitis occurred at this institution, with none attributable to drug failure. Adverse reactions, skin rashes mainly, were noted in 43 patients, and one patient died with Stevens-Johnson syndrome. These results confirm the efficacy of sulfamethoxazole-trimethoprim in preventing P carinii pneumonitis in childhood cancer patients and illustrate the feasibility of large-scale unstructured delivery of the combination to patients with malignant diseases frequently associated with this pneumonia.