Two 5- and 17-days old neonates with hypoplastic left heart syndrome respectively underwent orthotopic heart transplantation. The donor-recipient weight ratio was +58 percent and +88 percent; ischemic time was 144 and 167 min. The immunosuppressive protocol included thymoglobulin during the induction period and a classical 3-drug therapy, with a rapid tapering off of prednisone over 3 weeks. No infectious complication was observed; each infant experimented one episode of acute rejection, successfully treated with prednisolone. Forty-three months and 10 months later, the 2 children are doing well, with normal renal function and normal growth. No late rejection episode was observed. Heart transplantation in neonates is feasible, the short-term and mid-term results are good. Despite important ethical problems, heart transplantation represents a great hope for neonates with inoperable congenital heart defects.