Rats which were immunosuppressed with adrenal corticosteroids then transtracheally inoculated with Pneumocystis carinii were evaluated as models for study of drug efficacy. Trimethoprim/sulfamethoxazole, known to be effective against Pneumocystis, was given in therapeutic and prophylactic regimens and its long-term effectiveness determined by a protocol to study relapse. Untreated animals uniformly developed severe infection with differences in numbers of organisms between untreated and treated animals being greater than two logs. Therapy of prophylaxis studies could be completed in 6 to 7 weeks. Animals given prophylaxis or therapy with trimethoprim/sulfamethoxazole had few organisms detected in lungs. Numbers of organisms did not increase during the 4 weeks when the animals were continued on immunosuppression after discontinuing treatment as long as reinfection was prevented. These models are useful for evaluating anti-Pneumocystis activity of antimicrobials. Relapse study data suggest that reinfection may have an important role in development of recurrent Pneumocystis pneumonia.