Activins are growth factors involved in the control of cell proliferation and differentiation. Human breast tissues express immunoreactive activin subunits, and activin A is able to inhibit the replication of mammary cells in vitro. The aim of the present study was to evaluate 1) whether breast cancer expresses activin betaA subunit mRNA, 2) whether serum activin A levels are altered in postmenopausal women with breast cancer, and 3) how circulating activin A levels change after tumor removal. Four groups of women (n = 158) were enrolled for the present prospective study: two groups were composed of postmenopausal women with breast cancer (n = 74) or benign lesions (n = 15); the third was a control group composed of healthy postmenopausal women (n = 62); and the fourth group included healthy fertile women (n = 7) undergoing plastic surgery with removal of non-neoplastic mammary tissue. RT-PCR showed that betaA subunit mRNA was expressed in breast carcinoma, fibroadenoma, and normal mammary tissue, and the level of expression was higher in carcinoma than in normal tissue (P < 0.05). Dimeric activin A was detectable in homogenates of breast cancer tissue at concentrations twice as high as in non-neoplastic tissue (P < 0.01). In women with breast cancer, median serum activin A levels were significantly higher than in controls (P < 0.001). The high serum activin A levels in patients with breast cancer were not correlated with the presence of lymph node metastasis, tumor grade, or tumor diameter. After tumor excision, a significant decrease of activin A in the first and second postoperative days was observed (P < 0.01; Friedman's ANOVA). Conversely, activin A levels remained unchanged after plastic surgery in healthy women. The present results suggest that activin A is expressed and secreted in postmenopausal women with breast cancer. The pathophysiological and possible clinical implications of this finding remain to be investigated.