Plasma lipids, lipoprotein and apolipoprotein levels were determined in seven women and seven men with moderate obesity before, during 7 weeks of continuous weight loss (10.4% to 9.6% of body weight, 1000 kCal/day diet), and after 3 months at a stable, reduced weight. Plasma triglyceride levels decreased by 30.4% in men and by 39.4% in women (p < 0.0001) after 1 week of caloric restriction and remained at this level throughout the study period. The plasma cholesterol decreased by 19.0% in men (p < 0.001) and by 10.9% in women (p < 0.01) in the period of active weight loss, but returned to prediet values after stabilization at a leaner body mass. Similar changes were observed in LDL cholesterol levels. No change in high density lipoprotein (HDL) cholesterol levels occurred during active weight reduction, but after 3 months at a reduced weight, a significant increase in HDL cholesterol was evident, and the ratio of HDL cholesterol to plasma cholesterol increased over prediet values (p < 0.001, women). Separation of HDL subpopulations by zonal ultracentrifugation before and after weight reduction revealed that HDL2 increased slightly in men and decreased slightly in women. In both genders, HDL3 tended to decrease after weight reduction. Plasma levels of apolipoprotein A-I decreased during active weight loss, but this was significant only in women (p < 0.05). After 3 months of reduced weight, plasma apo A-I increased to prediet levels. No significant changes in plasma apo A-II or apo E were noted. Our results indicate that in moderately obese, but otherwise healthy, subjects weight reduction achieved by caloric restriction does not affect HDL composition or subpopulation distribution significantly. Moreover, maintenance of a leaner body mass has a beneficial long-term effect by increasing HDL cholesterol and decreasing plasma triglycerides.