OBJECTIVE: To determine whether long-term maintenance treatment for toxoplasmosis protects against Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Cohort study. SETTING: Switzerland. PATIENTS: A total of 453 patients with human immunodeficiency virus (HIV) entered the Swiss HIV Cohort Study. Ninety-nine patients with cerebral toxoplasmosis but no previous or simultaneous P. carinii pneumonia were compared with 240 patients with AIDS and other severe opportunistic infections (Centers for Disease Control [CDC] stage IVC1 infection other than toxoplasmosis and P. carinii pneumonia) as well as with 114 patients receiving inhaled pentamidine in a study of primary pneumocystis prophylaxis in patients infected with HIV. MEASUREMENTS: Life-table analysis for P. carinii-free survival. MAIN RESULTS: Six of 99 (6%) patients with toxoplasmosis, 50 of 240 (21%) patients with other severe opportunistic infections, and 8 of 114 (6%) patients receiving inhaled pentamidine developed P. carinii pneumonia. Life-table analysis showed that the incidence of pneumonia was substantially lower in patients with toxoplasmosis compared with that in patients with other severe opportunistic infections and was similar to the incidence in patients receiving pentamidine as prophylaxis. Analysis of the medication records from patients with toxoplasmosis showed that pyrimethamine and sulfonamides were administered 50% of the time; pyrimethamine and clindamycin, 25% of the time; and pyrimethamine alone, 9.9% of the time but that only one of the six patients with toxoplasmosis who developed P. carinii pneumonia received pyrimethamine and sulfonamides in the month before diagnosis. CONCLUSION: Patients with cerebral toxoplasmosis have a low risk for subsequently developing P. carinii pneumonia. This decreased risk is probably the result of chronic suppressive treatment with pyrimethamine and sulfonamides.