Serum cholesterol rises with age in most Western (and Westernized) populations. To identify causes of this rise, the authors studied 315 young Dutch men in 1976 in the district of Utrecht, The Netherlands, when they were aged 18 or 19 years, and again in various towns in the same region 10 years later, in 1986. These men formed the lower and upper quartiles of the distribution of changes in body mass index (weight (kg)/height (m)2) from 1976 to 1986 in a larger cohort of men representative of all Dutch men aged 18 or 19 years in 1976. In 10 years, mean serum total cholesterol (+/- standard deviation) had increased by 1.20 +/- 0.88 mmol/liter (46 +/- 34 mg/100 ml), and high density lipoprotein (HDL) cholesterol had decreased by 0.12 +/- 0.21 mmol/liter (4.6 +/- 8.1 mg/100 ml). The mean increase in body mass index was 2.7 +/- 2.5 kg/m2, and the mean increase in body fat percentage (assessed from skinfolds) was 3.3 +/- 4.6 g/100 g. The mean subscapular:tricipital skinfold thickness ratio--an indicator of body fat distribution--had not changed. In multiple regression analysis, the change in body mass index was the only significant (p less than 0.001) determinant of changes in serum total cholesterol; an increase of 1 kg/m2 in body mass index was associated with an increase of 0.20 mmol/liter (standard error, 0.02) in serum total cholesterol. Changes in body mass index and in smoking habits both contributed significantly toward explanation of changes in HDL cholesterol and in the HDL cholesterol:total cholesterol ratio. If smoking habits were adjusted for, HDL cholesterol decreased by 0.02 mmol/liter and the HDL cholesterol:total cholesterol ratio decreased by 0.012 (standard error, 0.001) for every 1 kg/m2 increase in body mass index. Changes in body fat distribution, as assessed by skinfold ratio, were not associated with changes in lipids. By interpolation, the authors estimated that for the full cohort of men, including the second and third quartile of body mass index changes, the mean rise in cholesterol had been 1.15 mmol/liter (44 mg/100 ml), of which 0.47 mmol/liter could be explained by the estimated rise in body mass index of 2.4 kg/m2. An increase in body fatness between ages 19 and 29 years is a powerful determinant of the rise in total cholesterol and the fall in HDL cholesterol occurring over that period of time.