Between May 1988 and July 1991, 28 neonates and children underwent orthotopic heart transplantation at Children's Memorial Hospital in Chicago. Indications for heart transplantation were hypoplastic left heart syndrome (10), dilated cardiomyopathy (13), aortic stenosis with endocardial fibroelastosis (1), complex D-transposition of the great arteries after Senning repair (1), L-transposition of the great arteries with single ventricle after shunt (1), cor biloculare, pulmonary atresia, and situs inversus after Fontan (1), and chronic rejection after heart transplantation for hypoplastic left heart syndrome (1). The age at time of transplantation ranged from 2 days to 17 years (mean, 5.3 +/- 6.1 years). Early deaths were from intraoperative donor right ventricular failure (2) and acute rejection after a second transplant procedure at 21 days (1), for an in-hospital mortality rate of 10.7%. Immunosuppression was with cyclosporine, azathioprine, and prednisone, with an attempt to discontinue the prednisone in neonates at age 6 months as guided by endomyocardial biopsy. Rejection episodes were treated with methylprednisolone pulse (34) or with OKT3 (4). Endomyocardial biopsy (in patients older than 6 months) was used extensively, and acute rejection was diagnosed in 29 of 301 biopsies. Three late deaths occurred (mean follow-up, 16.3 +/- 11.8 months): one of acute rejection at 13 months, one of viral pneumonia at 7 months, and one of intraabdominal sepsis as a complication of peritoneal dialysis at 5 months. Actuarial survival at 2 years is 77% +/- 9% (standard error of the estimate). Heart transplantation for neonates and for children can be performed with acceptable operative mortality. Intermediate results with triple therapy immunosuppression and an intensive rejection surveillance regimen relying on endomyocardial biopsy are encouraging.