Although triple-drug immunosuppression (cyclosporine, azathioprine, and prednisone) has reduced the incidence of acute rejection after pediatric cardiac transplantation, its effect on the development of coronary artery disease, which may be the major determinant of long-term survival in these patients, is not well defined. We reviewed 42 coronary angiograms obtained annually in 17 cardiac transplant recipients, aged 6 months to 18 years (mean, 12.4 years) at the time of transplantation, who had been maintained on triple-drug immunosuppression and had survived at least 1 year after transplantation. Each angiogram was reviewed for luminal irregularities or discrete stenoses, for the loss of third-order branching, and for the presence of myocardial bridging or calcification of vessels. Patient files were reviewed for donor and recipient age, sex, and ABO blood group, for postoperative episodes of rejection or cytomegalovirus infection, for hypertension, and for cholesterol and triglyceride values. No recipient in our series has died or undergone retransplantation because of coronary artery disease. Six of 17 (35%) patients have developed angiographically identifiable coronary artery abnormalities: four by the first year and two additional recipients by the second and third years, respectively, after transplantation. Development of coronary artery abnormalities approached a significant correlation when related to posttransplantation cytomegalovirus infection (p = 0.11) and older recipient age (p = 0.056) but not to any other factors studied, including episodes of rejection (p = 1.0). Angiographically identifiable coronary artery abnormalities can occur in pediatric recipients within the first year after cardiac transplantation in spite of a low incidence of acute rejection. Although the abnormalities may be mild initially, they can progress and require intervention.(ABSTRACT TRUNCATED AT 250 WORDS)