We studied male/female differences in serum lipids in randomly selected 38-year-old men (n = 337) and women (n = 342) from various cities in The Netherlands, Sweden, Italy, and Poland. Overall, men had higher triglycerides and total cholesterol levels and lower HDL-levels compared to women (P < 0.001). Adjustment for smoking habits, city, and body mass index did not remove the gender difference. Further adjustments for waist circumference alone and waist/hip and waist/thigh circumference ratio removed the gender differences in serum triglycerides and total cholesterol. Only adjustment for waist/thigh ratio removed the gender difference in HDL-cholesterol but linear relationships were different in men and women. The average male/female difference in serum lipids, particularly for total and LDL-cholesterol varied considerably among centers. In analyses of the data from the separate centers we found that sex differences in serum triglycerides and HDL-cholesterol in all 4 centers disappeared when adjusted for waist circumference alone and for waist/hip and waist/thigh ratio. For total and LDL-cholesterol, however, adjustment for circumference ratios tended to increase the male/female difference in 2 of the 4 centers. It is concluded that, in European men and women, fat distribution may be responsible for male/female differences in serum triglycerides but that such conclusions are less clear for HDL-, total- and LDL-cholesterol.