Between January 1987 and June 1988, 57 patients underwent heart transplantation (group 1: follow-up 6-36 months: mean 17.3 months). Immunosuppressive therapy consisted of cyclosporine (CsA), azathioprine (AZA), and low-dose steroids, plus prophylactic antilymphoblast globulin (ALG). Twenty-two patients (39%) developed clinically significant, proven cytomegalovirus (CMV) disease. All received monotherapy with intravenous ganciclovir. Six had concomitant pulmonary infections with other organisms, 4 of which were due to Pneumocystis carinii (PC). Overall mortality was 18%, possibly directly related to CMV infection in one case. Between July 1989 and October 1991 inclusive, 50 patients underwent heart transplantation (group 2: follow-up 3-31 months; mean 15.8 months). Immunosuppressive therapy consisted of CsA, AZA and high-dose steroids, with no ALG. CMV prophylaxis was given to every patient in the form of oral acyclovir for 3 months (at approximately 50 mg/kg/day) and commercially available immunoglobulin (500 mg/kg i.v. on days 7 and 35). Prophylaxis against PC was by trimethoprim/sulfamethoxazole (1 double-strength tablet/day) indefinitely. Only 2 patients (4%) in group 2 developed CMV disease (p < 0.001 vs group 1); none developed PC infection. Overall mortality was 4% (p < 0.03 vs group 1), possibly associated with CMV infection in one case. The incidence of acute rejection requiring extra therapy in the first 3-month period was 0.47 episodes/patient in group 1 and 0.24 episodes/patient in group 2 (p < 0.01). We conclude that CMV (and PC) infections can be largely prevented in heart transplant recipients.