A study was undertaken in 76 patients on maintenance hemodialysis and 26 patients on maintenance peritoneal dialysis to elucidate the pathogenesis of hyperlipidemia in these patients. A high prevalence of hypertriglyceridemia and low concentrations of high density lipoprotein cholesterol was found. Hemodialysis patients had low or normal total cholesterol concentrations which were significantly lower than those on peritoneal dialysis. The length of treatment did not affect the prevalence of the lipid abnormalities. Both pre- and post-heparin fractional clearance rates of Intralipid were markedly reduced in both groups of dialysis patients and were correlated inversely with serum triglyceride concentrations. However, when compared with normal subjects with similar fractional clearance rates of Intralipid, both groups of dialysis patients had higher serum triglyceride concentrations, probably reflecting increased triglyceride production. Serum triglyceride concentrations in both groups of dialysis patients were positively correlated with plasma immunoreactive insulin levels. Furthermore, a significant inverse correlation was observed between plasma immunoreactive insulin levels and post-heparin fractional clearance rates of intralipid. It was concluded that insulin resistance probably caused the defective triglyceride removal, and that both decreased removal and increased production of triglycerides contributed to the hyperlipidemia in dialysis patients.