Accelerated coronary atherosclerosis is a major cause of morbidity and death in the cardiac transplant recipient. Hypercholesterolemia has been implicated as a contributing risk factor. Because of this we reviewed lipoprotein profiles from transplant recipients from 1968 to 1986 in an attempt to identify the risk factors for the development of lipid disorders after transplantation. Patients were divided into three groups based on their immunosuppressive protocols. Group 1 consisted of 10 patients receiving azathioprine and prednisone. Group 2 consisted of 24 patients receiving cyclosporine and prednisone with or without azathioprine. Group 3 consisted of 18 patients receiving cyclosporine and azathioprine without prednisone. Total cholesterol levels at 1 year were highest in group 2 (266 mg/dl versus 236 mg/dl for group 1 [p = 0.16] and 223 mg/dl for group 3 [p = 0.005]). High-density lipoprotein cholesterol levels were lowest in group 3 (38 mg/dl versus 51 mg/dl for group 1 [p = 0.025] and 54 mg/dl for group 2 [p = 0.0001]). Subgroup analysis with multivariate and univariate analysis found that prednisone and preoperative coronary artery disease are the major contributors to the posttransplant lipid abnormalities.