The present immunohistochemical study examines the expression of TGF alpha, EGF, and the EGF receptor in prostatic tissues obtained from patients with either benign prostatic hyperplasia (BPH) or adenocarcinoma of the prostate. Frozen sections were cut at 5 microns and were incubated with monoclonal antibodies directed against TGF alpha, EGF, or the EGF receptor. The remainder of the staining procedure was performed with an avidin-biotin-complex peroxidase procedure. Strong TGF alpha expression was not detected in any of the 15 BPH specimens examined or in the normal/hyperplastic tissue intermixed within the adenocarcinomas. In contrast, malignant cells in 9 of 11 adenocarcinomas strongly expressed TGF alpha. EGF reactivity was observed in both hyperplastic and malignant epithelial tissues. EGF receptor expression was strongest along the basal aspects of cells of normal or hyperplastic glands. Although most malignant cells also were positive for the EGF receptor the level of staining was less than that observed in cells forming normal or hyperplastic glands. These results suggest that EGF and the EGF receptor may be components of an autocrine/paracrine regulatory pathway involved in hyperplastic and/or malignant disease of the prostate. The finding that TGF alpha is expressed only in malignant cells suggests that TGF alpha may represent a locally active autocrine regulator of malignant prostate cells.