The exact nature and significance of posttransplant hyperlipidemia is controversial. In the present study, serum lipids were examined in 201 clinically stable renal transplant recipients before, 1 year after, and at the time of the last follow-up, 5.0 +/- 0.1 yr after transplantation. Hypertriglyceridemia, present in 36% of patients treated with dialysis before transplantation, occurred in 23% 1 year after successful transplantation. At last follow-up, 29% had elevated triglyceride levels. Hypercholesterolemia, present in only 8% of patients before transplantation, was found in 27% 1 year after receiving a renal allograft. At the time of last follow-up, 30% had elevated cholesterol levels. HDL cholesterol levels were normal 1 year after transplantation, and increased significantly during the posttransplant follow-up period. Multivariate stepwise linear regression analysis was used to determine factors independently associated with serum lipid levels. Age, body weight, pretransplant serum lipids, and variables linked to allograft function (urine protein excretion, serum creatinine, and the use of loop diuretics) were independently associated with posttransplant cholesterol and triglycerides. Diabetes, the use of alternate day steroids, beta-adrenergic-blocking antihypertensive medications, and thiazide diuretics were not linked to hyperlipidemia. In addition, changes in variables associated with renal function helped to explain why different factors were associated with lipid levels at 1 year than at the time of last follow-up. Thus, the results of this study suggest that hyperlipidemia is a frequent and persistent complication in clinically stable renal transplant recipients. Multiple factors, including several associated with declining allograft function, appear to be involved in the pathogenesis of posttransplant hyperlipidemia.