We conducted a prospective, randomized clinical trial among liver transplant patients to assess the efficacy and safety of weekly sulfadoxine/pyrimethamine compared with daily trimethoprim-sulfamethoxazole in the prevention of Pneumocystis carinii pneumonia. The studied drugs were given during 6 months after transplantation. One hundred twenty patients were included. None of the 60 patients receiving weekly sulfadoxine/pyrimethamine developed Pneumocystis carinii pneumonia, whereas two cases (3%) developed among the 60 patients who received trimethoprim-sulfamethoxazole. For both patients, the studied medication had been discontinued several weeks earlier because of adverse effects. No differences were observed in the incidence of adverse effects. We conclude that weekly sulfadoxine/pyrimethamine is as effective and safe as is daily trimethoprim-sulfamethoxazole in the prophylaxis of Pneumocystis carinii pneumonia after liver transplantation.