The combination therapy of oral etoposide and estramustine phosphate (EMP) showed promising results for the treatment of hormone-refractory prostate cancer. Binding of EMP to microtubule-associated proteins, tubulin and proteins of the nuclear matrix are currently considered to be the most likely mechanisms underlying the cytotoxicity in androgen-independent prostatic carcinoma. Combination of EMP with etoposide has produced antitumour responses in 30±60% of patients with metastatic hormonerefractory prostate carcinoma. In vitro, EMP and etoposide (VP-16) appeared to act synergistically to inhibit the growth of the metastatic human prostate adenocarcinoma cell line PC3. Transforming growth factor b(TGF-b) is growth inhibitory to many malignant cells, including prostate cancer cells. We have previously shown that TGF-b plays a signi®cant role in PC3 cell growth inhibition. This study aimed to de®ne the possible association of activity of antineoplastic agents with TGF-b protein in hormone-refractory prostate cancer cell lines.