The distribution and structure of high density lipoprotein (HDL) subfractions were examined by rate zonal ultracentrifugation in 200 consecutive subjects, 86 of whom showed a stable hypertriglyceridemia, 22 with coronary artery disease. Among the remaining 114 normotriglyceridemic subjects, 75 were healthy and 39 had coronary disease. The serum levels of the HDL2 subfraction were reduced by 22% in the 39 normotriglyceridemic coronary patients, and by 21% in the whole group of hypertriglyceridemic subjects. No difference in the HDL3 levels was found in any of the studied group. There was a clear negative correlation between HDL2 levels and triglyceridemia in the case of healthy people, not in coronary patients. By contrast, triglyceridemia was negatively correlated with the HDL3 flotation rate, both in healthy subjects and coronary patients at all triglyceride levels. Compositional data indicate that in hypertriglyceridemic subjects, HDL2 levels are reduced because of an enhanced transfer-exchanged process between the enlarged VLDL pool and HDL; in contrast, in coronary patients, a defective maturation of the HDL3 particle is the most likely underlying mechanism. Both in hypertriglyceridemic individuals, as well as in coronary patients, the HDL subfraction distribution is rather similar and drastically different from that of normotriglyceridemic healthy subjects. The mechanisms of the two conditions are probably different and, whereas a low concentration of HDL2 is definitely a major risk factor for normotriglyceridemic individuals, in the case of hypertriglyceridemics other factors may come into play in the final determination of the coronary risk.