Chronic rejection is the leading cause of late allograft failure, but its pathogenesis is poorly understood. The prominence of the vascular lesions and certain similarities with the pathological features of atherosclerosis suggest that lipids may be involved in the pathogenesis of chronic rejection. Studies have reported an association between different lipid abnormalities and several indicators of chronic renal allograft damage. However, other potential risk factors for the development of chronic rejection were present in most cases, and an independent association between lipids and chronic rejection has not been convincingly demonstrated. In our series of 706 consecutive renal transplants with long-term follow-up, increased post-transplant serum triglycerides, but not total cholesterol, were strong predictors of graft loss to chronic rejection. This effect was independent of other risk factors for chronic rejection such as age, acute rejections, proteinuria and hypoalbuminemia. These results add to existing evidence suggesting that lipid abnormalities may be involved in the pathogenesis of chronic renal allograft rejection.