Data on the presence of oxytocin receptors (OTR) within the prostate are still controversial and variable among different species. In the present study, OTR expression and localization has been investigated in human hyperplastic and neoplastic prostate at mRNA and protein levels using in situ hybridization (ISH) and immunohistochemistry (ICC) techniques, respectively. In all the cases studied, epithelial cells expressed OTR mRNA and protein. Interestingly, this expression was more intense in neoplastic epithelial cells compared to the hyperplastic ones. In order to determine whether OTR might mediate a biological effect of oxytocin (OT) in prostate cancer cells, OTR expression was studied by RT-PCR and immunofluorescence technique in the human androgen-independent prostate cancer cell line DU145. In addition, a possible heterotopic production of OT by DU145 cells was studied using RT-PCR. The data obtained showed that DU145 cells expressed OTR, whereas no OT mRNA was detected. When DU145 cells were treated with OT (100 nM) a significant inhibition of cell proliferation was observed, while co-incubation with the OT antagonist OTA (100 nm) abolished such an effect. The involvement of apoptosis in the OT effect contrasting cell proliferation was excluded by ISEL technique, which revealed a similar pattern of DNA fragmentation in either untreated or OT-treated cells. Altogether, the data indicate that the OT/OTR system could be involved in the control of prostate neoplastic pathology.