Pathologic conditions of six long-term orthotopic heart transplant survivors (11 to 17 years) was compared with a group of six similar heart transplant recipients surviving only 2 years. The two groups were matched as far as possible for age and sex of both recipients and donors and for immunosuppressive therapy (azathioprine and prednisone). Ischemic time, HLA-A, -B typing, acute rejection episodes, lipid profiles, and coronary angiograms were investigated in both groups. None of these parameters correlated with survival or disease of the graft. Graft coronary disease was present in 10 of 12 cases and caused graft failure in 8 of 12. All six long-surviving grafts and four of six surviving only 2 years showed occlusive coronary disease. The major difference in the two groups was in the pathologic condition of the coronary arteries in the long-term survivors, which more resembled that of naturally occurring atherosclerosis than the characteristic concentric graft coronary disease present in grafts surviving 2 years. Although the histopathologic features were different in the two groups, no investigated factor was useful in predicting graft disease and survival.