Objective: To evaluate the course of changes in serum inhibin A, inhibin B, and pro-alphaC levels in women with surgically or pharmacologically induced menopause. Design: Longitudinal study. Setting: Academic Health Center of Siena, Siena, Italy. Patient(s): Four groups of women were studied: [I] surgical menopause including bilateral oophorectomy (n = 15), [2] amenorrhea induced by GnRH-analogue for treatment of endometriosis (n 13), [31 amenorrhea induced by antineoplastic chemotherapy before (n = 15) and after chemotherapy (n 13), and [4] control physiological menopause (n = 67). Intervention(s): Collection of blood specimens. Main Outcome Measure(s): Serum inhibin A, inhibin B, and pro-alphaC concentrations were measured by using specific two-site ELISAs. Result(s): Following oophorectomy, serum inhibin A, inhibin B, and pro-alphaC levels were decreased on the first postoperative day; on the fifth postoperative day they were still significantly reduced. Women with amenorrhea induced by GnRH-analogue treatment exhibited serum inhibin A and pro-alphaC levels that were significantly higher than those observed in physiological menopause. Patients undergoing antineoplastic chemotherapy had higher serum inhibin A levels than those in physiological menopause, whereas inhibin B C and pro-alphaC levels did not differ. During the course of chemotherapy, median serum inhibin A concentrations were similar to those of patients evaluated after the suspension of treatment. In postmenopause, inhibin A, and inhibin B levels were low, whereas levels of pro-alphaC were still detectable. Conclusion(s): Circulating levels of inhibin A, inhibin B, and pro-alphaC are reduced after oophorectomy. Women with amenorrhea induced by GnRH-analogue treatment or by antineoplastic chemotherapy still produce inhibin A and pro-alphaC. This probably reflects a residual ovarian function and hormone synthesis. Therefore, the ovary may be a source of pro-alphaC after menopause; significant amounts of pro-alphaC are present in circulation after natural menopause, but not after oophorectomy.