BACKGROUND. Epithelial cells from the human benign prostate express melatonin receptors which effect transient suppression of DNA synthesis and sustained attenuation of growth. The role of transforming growth factor-1 (TGF1), which is produced in prostate epithelial cells and inhibits their growth, was examined in the action of melatonin. METHODS. The effects of melatonin and TGF1 and their combination on 3 H-thymidine incorporation were assessed. The possibility that melatonin effected TGF1 release from cells was studied. RESULTS. Incubation of the cells with TGF1 resulted in a time-and dose-dependent inhibition of 3 H-thymidine incorporation into cells. Melatonin (10-500 pM) inhibited 3 Hthymidine incorporation, and its effects were attenuated at higher (1-10 nM) concentrations. In the presence of submaximal doses of TGF1, the inhibitory effect of melatonin was maintained over the entire concentration range tested (10 pM-10 nM). The inhibition of 3 Hthymidine incorporation by TGF1 was more pronounced in the absence of dihydrotestosterone (DHT) than in its presence, and melatonin had no further effect. Melatonin enhanced the release of proteins from cells, among them proteins recognized by specific TGF1 antisera. The TGF1-neutralizing antisera prevented the inhibitory action of melatonin on 3 Hthymidine incorporation into cells. CONCLUSIONS. These data indicate a role for TGF1 in the melatonin-mediated attenuation of benign prostate epithelial cell growth.