To elucidate the pathogenesis of hyperlipidemia in chronic renal disease in children and adolescents, we have measured serum triglyceride, total cholesterol, high density lipoprotein cholesterol (HDL-C) and activities of postheparin plasma lipoprotein lipase and hepatic triglyceride lipase (EC 3.1.1.3) in nine patients with transplants, and nine hemodialyzed and 18 conservatively treated patients with chronic renal failure. In 29 of 36 patients, serum insulin levels both in fasting and in response to oral glucose load were measured. The lipase activities were measured separately, utilizing antiserum against hepatic triglyceride lipase.All groups of patients had hypertriglyceridemia. The patients with endogenous creatinine clearance less than 20 ml/min/m2had a low HDL-C level. The HDL-C level was correlated inversely with serum triglyceride level and positively with glomerular filtration rate. The lipoprotein lipase activities were low in patients with endogenous creatinine clearance less than 20 ml/min/m2. Although hepatic triglyceride lipase activities were not significantly low in any groups of patients, they were correlated with glomerular filtration rates in the conservatively treated patients with chronic renal failure. A defective triglyceride removal due to low lipase activities may contribute to uremic hypertriglyceridemia in these patients. On the other hand, patients with transplants had almost normal lipase activities and exhibited hyperinsulinemia; overproduction of triglyceride due to hyperinsulinemia may contribute to their hypertriglyceridemia.