Serum inhibin levels are elevated in postmenopausal women with granulosa and mucinous epithelial tumors of the ovary. In contrast, functional deletion of the inhibin alpha gene in male and female mice results in the development of primary gonadal granulosa/Sertoli cell tumors. The aim of this study was to determine whether inhibin alpha-subunit gene and protein expression are altered in prostate cancer. Messenger ribonucleic acid expression was studied by in situ hybridization, and protein localization was studied by immunohistochemistry. Inhibin alpha-subunit messenger ribonucleic acid expression and protein localization were observed in the epithelium of tissues from men with benign prostatic hyperplasia, in regions of basal cell hyperplasia, and in nonmalignant regions of tissue from men with high grade prostate cancer. In the malignant regions of tissue from men with high grade prostate cancer, the expression of the inhibin alpha-subunit gene was suppressed and was not detectable in poorly differentiated tumor cells. These results demonstrate that in contrast to ovarian granulosa cell tumors, inhibin alpha gene expression is down-regulated in poorly differentiated prostate cancer.