The relationship between menopause and cardiovascular risk factors of progestin alone or in combination with estrogen were analysed in a sample of French women. Three thousand four hundred and forty consecutive women, between 45 and 65 years of age, who received a systematic check-up between January 1991 and April 1993 were enrolled in this study. All biological measurements were performed at a central laboratory. Women were classified as premenopausal (n = 1233), postmenopausal (n = 1774) if they had not menstruated in the 12 months before examination, and perimenopausal (n = 433) if they met at least two of the following criteria: elevated levels of serum follicle-stimulating hormone (FSH), irregular menses, amenorrhea for less than 12 months, hot flushes. The effect of menopause on cardiovascular risk factors was determined in 2167 women between 45 and 65 years of age (premenopausal n = 790, postmenopausal n = 1377), none of whom were presently treated with hormonal replacement therapy (HRT). In addition, the effect of progestin was assessed in a group or 397 perimenopausal women, and the effect of combined estrogen and progestin replacement therapy in another group of 1746 postmenopausal women. Menopause was associated with higher levels of serum cholesterol (6.4 vs. 5.9 mmol/l), triglycerides (1.2 vs. 1.0 mmol/l), apolipoprotein (apo) B (1.3 vs. 1.1 g/l), apo A-I (1.9 vs. 1.8 g/l), as well as with elevated diastolic blood pressure (79.7 vs. 77.0 mmHg). Multivariate analysis indicated that these effects were independent of age, body mass index (BMI), glycemia, smoking, alcohol intake, exercise and parity. Perimenopausal women treated with progestin alone (n = 95) were compared to perimenopausal women not using HRT (n = 302). There were no statistically significant differences in the levels of cholesterol, triglycerides, apo B, apo A-I, glycemia and blood pressure between the two groups. Postmenopausal women using a combination of estrogen and progestin (n = 369) had significantly lower levels of serum cholesterol (6.1 vs 6.4 mmol/l), triglycerides (1.0 vs. 1.2 mmol/l), apo B (1.2 vs. 1.3 g/l), systolic (131.9 vs. 137.9 mmHg) and diastolic (76.9 vs. 79.7 mmHg) blood pressure than postmenopausal women without hormonal therapy (n = 1377), taking into account confounding variables. In contrast, serum apo A-I levels were not altered by the combined hormonal therapy. We conclude that menopause is associated with the aggravation of multiple cardiovascular risk factors. These deleterious factors are affected by a treatment of combining estrogen and progestin.