We investigated the effect of the menopause and postmenopausal hormone replacement therapy on the serum concentration of carboxyterminal propeptide of type I procollagen (PICP), which is a biochemical marker of type I collagen synthesis. A group of 124 healthy postmenopausal women, aged 45-53 years, had about 20% higher serum PICP than did a group of 40 healthy premenopausal women aged 35-52 years (114 +/- 35 micrograms/l vs. 95 +/- 26 micrograms/l (mean +/- SD); p = 0.002). The 124 postmenopausal women were also participating in a double-masked longitudinal study with two placebo groups and four different hormone replacement therapy groups. The four hormone regimens resulted in similar responses in serum PICP. Compared with placebo, 1 year of treatment with any of the four hormone replacement therapies significantly decreased serum PICP to premenopausal levels. We conclude that the formation of type I collagen is increased shortly after the menopause and that hormone replacement therapy reverses this increase.