We compared plasma lipid and lipoprotein parameters between 210 chronic renal failure patients treated by hemodialysis and 223 age- and sex-matched healthy control subjects to examine whether atherogenic lipoprotein changes were present in hemodialysis patients in the absence of hyperlipidemia. The hemodialysis group showed higher levels of plasma triglycerides, very low density lipoprotein (VLDL) cholesterol, and intermediate density lipoprotein (IDL) cholesterol and a lower level of high density lipoprotein (HDL) cholesterol. Low density lipoprotein (LDL) cholesterol of the hemodialysis group was not elevated but their LDL was significantly more triglyceride-enriched than that of controls. Subjects were then divided into five categories according to their plasma triglyceride levels at an interval of 50 mg/dl, and comparison was made between the two groups in the same range of plasma triglycerides. Hemodialysis patients again showed higher levels of VLDL- and IDL-cholesterol, and lower levels of HDL-cholesterol than the control group even in the plasma triglycerides-matched comparisons. Similarly, higher VLDL- and IDL-cholesterol levels in hemodialysis patients were significant in plasma total cholesterol-matched subgroup comparisons. Multiple regression analysis indicated that the relationship between plasma lipid concentrations and individual lipoprotein levels were substantially altered in uremic state. The 95th percentile level of IDL-cholesterol in the nonuremic controls was 15 mg/dl, and 45% of hemodialysis patients exceeded this level. Decreased HDL-cholesterol levels < or = 35 mg/dl were seen in 6% of the control and 38% of the hemodialysis group. Elevated IDL-cholesterol and decreased HDL-cholesterol were persistently found in hemodialysis patients with normal lipid levels. It is concluded that hemodialysis patients exhibited more atherogenic lipoprotein profile than nonuremic subjects with comparable levels of plasma triglycerides and total cholesterol. Especially, increased IDL- and decreased HDL-cholesterol levels in hemodialysis patients persisted even at very low levels of plasma lipids. Since elevated IDL and decreased HDL-cholesterol are implicated in the progression of atherosclerosis, these findings are of clinical importance in the diagnosis of lipoprotein disorder in chronic renal failure.