Effects of chronic ethanol consumption on serum lip–oproteins have been studied in the rat. The serum levels of triglycerides, cholesterol, phospholipids and apolipo-proteins AI and AIV increased significantly after 1 week of ethanol feeding, and they remained elevated up to 7 weeks of alcohol drinking. By contrast, serum total apolipoprotein E decreased or, sometimes, did not change. Very-low-density lipoprotein cholesterol, triglycerides and very-low-density lipoprotein apolipoprotein E of the alcohol-fed rats increased in parallel and were about 2-to 2.5-fold over the controls. Whereas high-density lipoprotein cholesterol, phospholipids, apolipoprotein AI and AIV increased 1.2-fold by chronic alcohol feeding, the level of high-density lipoprotein apolipoprotein E decreased to 70% of that of the control rats. The rates of secretion of apolipoprotein AI, E and AIV into the culture medium by hepatocytes isolated from ethanol-fed rats were 1.8-, 1.3-and 1.1-fold higher than those from control rats. These data indicate that (i) chronic ethanol feeding increases very-low-density lipoprotein and high-density lipoprotein in the rat; (ii) serum high-density lipoprotein particles of the ethanol-fed rats are deficient in apolipoprotein E, and (iii) chronic ethanol feeding increases hepatic secretion of apolipoprotein AI, E and AIV. Since the steady-state serum level of apolipoprotein E decreases or remains unchanged in the presence of increased hepatic apolipoprotein E secretion, this imbalance suggests that alcohol feeding either accelerates the rate of degradation of serum apolipoprotein E or suppresses apolipoprotein E synthesis by nonhepatic tissues.