Transforming growth factor-beta (TGF-beta1) is a potent negative regulator of cell growth that transduces signals through interactions with type I and II receptors. Abnormal expression and mutational alterations of these receptors have been observed in several human malignancies. In this study, we investigated the expression of the two types of TGF-beta1 receptors, R-I and R-II, in a normal human prostate, primary prostate adenocarcinoma and lymph nodes with metastatic deposits. Expression of receptor proteins was examined by immunohistochemical analysis in paraffin-embedded prostatic tissue sections, and mRNA expression was determined by Northern blot and RT-PCR analysis. Uniformly strong immunoreactivity for both TGF-beta receptor proteins, R-I and R-II, was exclusively localized to the prostatic glandular epithelium of normal prostates. In contrast, tumor epithelial cells in primary and metastatic prostatic cancer specimens exhibited a weak heterogeneous immunoreactivity for both R-I and R-II receptors; 25% of primary prostatic tumors and 45% of the lymph nodes with metastases were totally negative for R-I and R-II expression, while the rest exhibited a significantly reduced immunoreactivity for both types of receptors compared to the normal prostate (p < 0.05). Moreover, there was a significant decrease in the expression of R-I and R-II mRNA, in all 20 primary prostatic tumors and 4 lymph nodes positive for metastases, indicating that the decreased protein expression was due to down-regulation of gene expression for the two receptors. Our findings imply that decreased expression of TGF-beta1 type I and type II receptors might be involved in prostate tumorigenesis.