Pediatric heart transplantation is entering its third decade, allowing for the first time an analysis of a large group of true long-term survivors, specifically children who have survived > or =10 years post-transplantation. Fifty-two patients < or =18 years, who had undergone heart transplantation at Stanford between August 1974 and June 1993 and survived > or =10 years, were retrospectively reviewed. Forty (77%) patients are currently alive. Thirteen survived >15 years and 5 >20 years (the longest being 26 years). Actuarial survival was 79.4% at 14 years and 53.1% at 20 years. Cardiomyopathy was the reason for transplantation in 71% and congenital heart disease (CHD) in 29%. At last evaluation, 71% were on a cyclosporine-based regimen and 23% a tacrolimus-based regimen; 33% were steroid-free. Twenty-seven percent were totally free from treatable rejection, 44% developed serious infections, 69% were receiving anti-hypertensives, and 8% required renal transplantation. Neoplasms occurred in 23%, graft coronary artery disease (CAD) in 31%, and 15% required re-transplantation. Of the 12 deaths, CAD was the most common cause (n = 4), followed by non-specific late graft failure (n = 3), infection (n = 2), rejection (n = 1), non-lymphoid cancer (n = 1) and lymphoid cancer (n = 1). Physical rehabilitation and return to normal lifestyle has been nearly 100%. Heart transplantation in pediatric patients is compatible with true long-term survival with a growing cohort of children approaching their second and third decades. The gradual constant-phase decrease in survival noted in earlier studies appears to be continuing. Rejection and infection are low but persistent risks after the first years. Graft CAD and non-specific late graft dysfunction are the leading causes of death after 10 years. Rehabilitation is excellent.