Pneumocystis carinii pneumonia (PCP) is an important infection in the setting of liver transplantation. Without prophylactic measures, the incidence of PCP reached 30% in our first 10 liver transplant patients. All patients but one, who had concomitant invasive aspergillosis, recovered with intravenous cotrimoxazole. We therefore prospectively studied, in an open clinical trial, the efficacy and safety of prophylaxis with daily low-dose cotrimoxazole (480 mg) in 60 patients. The incidence of PCP dramatically decreased to 1.7% (P<.01). Treatment was well tolerated, and discontinuation of therapy was only necessary in two patients with leukopenia. Nevertheless, the number of episodes of leukopenia was similar in both groups. Cotrimoxazole prophylaxis was not associated with increased nephrotoxicity. An overall benefit in the incidence of bacterial infection was not observed. We conclude that daily low-dose cotrimoxazole is effective and safe for prevention of PCP after liver transplantations.