The efficacy of clarithomycin and sulphamethoxazole for treatment of experimental Pneumocystis carinii infection was investigated. Rats were immunosuppressed with dexamethasone and inoculated intratracheally with 5 x 10(6) P. carinii cysts. After 2 weeks, the lung tissues were assayed for P. carinii cyst burden. The combination of clarithromycin and sulphamethoxazole caused a significantly greater reduction in cyst burden than either drug alone. Up to 50% of the rats treated with the combination of clarithromycin and sulphamethoxazole were negative for P. carinii cysts. Equivalent doses of the individual drugs given alone did not produce cures. The combination of clarithromycin and sulphamethoxazole was more than twice as effective as either drug alone. Clarithromycin combined with sulphamethoxazole in treatment of P. carinii infection could be especially useful since clarithromycin monotherapy provides safe and effective treatment against many other pathogens, including several that are associated with AIDS.