The relation between menopause and serum total and high-density-lipoprotein cholesterol was examined by the Minnesota Heart Survey in a cross-sectional, population-based study of 344 black women and 474 white women aged 35-54 years from the Twin Cities metropolitan area in 1985-1986. Analysis of covariance was used to examine differences in serum total and high-density-lipoprotein cholesterol in black women and white women by menopausal status, adjusting for the effects of age, educational level, cigarette smoking, body mass index, exercise, alcohol consumption, diabetes mellitus, sex hormone, beta blocker, and diuretic use. Among whites, adjusted serum total cholesterol was 13 mg/dl higher in postmenopausal than in premenopausal women (p less than 0.002). Black postmenopausal women had slightly higher serum total cholesterol than did their premenopausal counterparts (5.4 mg/dl). However, this was not statistically significant. An interaction term in a linear regression model confirmed a racial difference in the total cholesterol association with menopause (p less than 0.02). The higher total cholesterol levels observed in white postmenopausal women were mainly among those with natural menopause (20.7 mg/dl higher than premenopausal, p less than 0.0003) and those with a hysterectomy and at least one intact ovary (11.0 mg/dl higher, p = 0.05). Among black women, only the subgroup with a hysterectomy and a bilateral oophorectomy had a significantly higher serum total cholesterol (19.9 mg/dl higher than premenopausal, p less than 0.05). There was no significant association between high-density-lipoprotein cholesterol and any type of menopause in either black women or white women. Our findings may reflect a true physiologic difference in the relation between menopause and serum total cholesterol between American blacks and whites. The lack of a significant association between menopause and high-density-lipoprotein cholesterol in either race raises the possibility that menopause may not affect atherosclerosis risk via reduced high-density-lipoprotein cholesterol.