Because fetal urogenital sinus mesenchyme (UGM) has been found to be highly inductive when recombined with normal adult prostate tissues or normal and neoplastic bladder epithelium, we investigated whether fetal UGM also interacts with established hormone-responsive and unresponsive rat Dunning and Nb prostate tumors. Our results indicate that: 1) fetal UGM acts directly on selected rat prostatic tumors by inducing histomorphologic changes (e.g., inducing acinar ductal structures and secretory activity) in the tumors toward more differentiated forms resembling that of the adult prostate gland; 2) fetal UGM either increased the growth rate of or maintained the sizes of three of the four interacting rat prostatic tumors; and 3) fetal UGM markedly reduced the lactate dehydrogenase activity of Nb-autonomous tumor toward a level comparable to that of the normal rat prostate gland. Our data suggest that fetal UGM can directly affect the growth and differentiative functions of selected rat prostatic tumors.