Cardiac transplantation has only recently become an accepted therapeutic modality for children and adolescents with end-stage cardiomyopathy. Long-term survival, the incidence of rejection, and the incidence of infection are still being defined. From 1985 to 1989, 21 children aged 6 months to 19 years (average age, 11.2 years) underwent cardiac transplantation at our institutions. Eighteen survived the operative period and have been followed for 5 to 49 months (average follow-up, 24 months). All operative survivors have received tripledrug immunosuppression consisting of cyclosporine, azathioprine, and prednisone. During follow-up, 7 patients have been treated on 12 occasions for rejection as documented by endomyocardial biopsy. Eight (67%) of the 12 episodes of rejection occurred in the presence of subtherapeutic cyclosporine levels. Two of the 7 patients treated for rejection have subsequently died of ongoing cardiac rejection and arrhythmia. There have been no perioperative or late deaths from infection. Bacterial sepsis was identified and treated twice during follow-up, viral infections on five occasions, and fungal infection once. Actuarial 1-year survival and 3-year survival of the 18 operative survivors are 94% and 78%, respectively. In the first 7 months after cardiac transplantation, 73% of patients were free from rejection and 83% were free from serious bloodborne infection. We conclude that (1) the incidence of rejection and infection is low with tripledrug immunosuppression; (2) rejection episodes occur must commonly within the first year after cardiac transplantation but can occur late; (3) rejection can often be associated with subtherapeutic cyclosporine levels; (4) major bacterial infection can occur in association with a common disease process but appears to respond to standard antibiotic therapy; and (5) viral infections have been well tolerated by the patients.