We determined the time-dependent variations in biochemical estimates of bone resorption and bone formation in 30 healthy postmenopausal women treated for two consecutive cycles of 28 days with a sequential estrogen/gestagen therapy. The women received either 1, 2, or 4 mg estradiol (E2) for 22 days and 1 mg norethisterone acetate (NETA) from day 13 to 22 of each cycle. Blood samples were drawn twice a week, ie, 16 blood samples in each woman. Biochemical estimates of bone resorption (fasting urinary hydroxyproline/creatinine, fasting urinary calcium/creatinine) decreased significantly during the two treatment cycles. In contrast, there was no overall decrease in bone formation parameters (plasma bone Gla protein [pBGP], serum alkaline phosphatase), and serum alkaline phosphatase decreased significantly during the estrogen-only phase, but increased during the E2 plus NETA phase. The present study supports our previous suggestion that NETA stimulates bone formation in early postmenopausal women.