Interferon-gamma (IFN-gamma) was used to treat rats with steroid-induced Pneumocystis carinii pneumonia (PCP). Treatment with 427,000 U/day prophylactically prevented infection in this model. Treatment with 200,000 U, three times/week for 2 weeks caused a significant reduction in the number of cysts in the lungs and prolonged survival of the rats. In addition, IFN-gamma and trimethoprim/sulfamethoxazole behaved synergistically in the treatment of PCP in rats. Reduced dosages of each drug, when given together, caused an almost complete eradication of the infection. This may be a useful approach in patients with acquired immune deficiency syndrome in whom anti-Pneumocystis drugs are often toxic.