Immature rat ventral prostate was used to identify a potent cell growth inhibitory factor in normal prostate. Both conditioned media and peptide extracts derived from ventral prostates inhibit the cellular growth and DNA synthesis in metastatic androgen-independent human prostate carcinoma cell line (PC3). The prostatic inhibitory factor was partially purified using an hydrophobic HPLC column (C18). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis (SDS-PAGE) of partially purified material revealed a major 25-kDa band. Immunoblot analysis showed similarity of the inhibitory factor to the transforming growth factor-beta (TGF-beta). Furthermore, the proliferation inhibiting activity of the prostatic factor was completely abolished by anti-TGF-beta antibodies. These data indicate that normal prostate produces a TGF-beta-like protein under non-physiological conditions.