Recent studies have shown that heterogeneity of human plasma low-density lipoproteins (LDL) is, in part, the result of production of different LDL products from two subspecies of intermediate-density lipoproteins (IDL). Cholesterol-enriched forms of both IDL species are found in plasma of patients with atherogenic dyslipidemias (familial hypercholesterolemia and type 3 hyperlipoproteinemia) and have physical properties similar to the major species in plasma of cholesterol-fed monkeys. Patients with familial combined hyperlipidemia have been shown to have increased plasma levels of IDL and of a smaller, denser LDL subclass (LDL-IIIA) that appears to be a metabolic product of the smaller IDL subspecies. Results from the NHLBI Type II Coronary intervention study have supported a link between the small IDL-LDL pathway and coronary disease, In that 2-year changes in levels of these species were associated with disease progression. Furthermore, therapeutic reductions in IDL levels were correlated with increases in high-density lipoprotein cholesterol. Thus variation in IDL levels might influence coronary disease risk by both a direct effect and indirectly by affecting LDL particle number and possibly high-density lipoprotein metabolism.