In order to better define potential mechanisms of growth regulation in human prostate cancer cells, we have compared biological responses (such as short-term response to both transforming growth factor alpha and beta; TFG alpha and TFG beta) in relation to hormone sensitivity of LNCaP, DU145, and PC3 cells. Androgen receptor (AR) and epidermal growth factor receptor (EGF-R) content of each cell line was also investigated. In addition, expression of EGF, TGF alpha, and TGF beta was evaluated through immunofluorescent staining. Growth of androgen non-responsive PC3 cells was stimulated by TGF alpha (about 35%) and inhibited by TGF beta (more than 50%), with respect to controls, after 48 h exposure. Conversely, AR-positive, hormone-responsive LNCaP cells proved to be poorly sensitive, at least short-term, to either growth factor. Furthermore, high levels of both EGF-R and TGF alpha, and a fairly high amount of EGF, were found in DU145 cells and, to a lesser extent, in LNCaP cells; in contrast, PC3 cells exhibited low expression levels of both receptors (EGF-R) and ligands (EGF, TGF alpha), but displayed remarkable TGF beta binding and relatively high levels of endogenous TGF beta. Overall, these results suggest a differential sensitivity to TGF alpha and TGF beta by prostate cancer cells; TGF alpha response seems not to be proportional to the EGF-R content of individual cell lines.