Plasma lipid and high density lipoprotein (HDL) levels were studied in 20 normal, healthy, non-obese males while fasting (150 kcal/d with free intake of water) for 6 d in a hunger strike. Plasma triglyceride and cholesterol levels were increased by 18% after 6 d of fasting. HDL-cholesterol concentration was not significantly changed for 4 d, but decreased by 22% after 6 d. Platelet aggregation induced by adenosine diphosphate (ADP) or collagen after 6 d of fasting was in the normal range. In 3 subjects fasted for 9 d, a complete plasma lipoprotein analysis was done. Very low and low density lipoprotein (VLDL and LDL) levels were elevated, whereas HDL was reduced after 9 d of fasting. On isoelectric focusing analysis, a marked reduction in apolipoprotein (apo) E concentration in both VLDL and HDL was noted. Liver function tests showed a reduction in hepatic enzyme activity; and since apo E is of hepatic origin also, we suggest that long fasting inhibits liver function in normal subjects.