The purpose of this study was to determine if a cause-and-effect relationship exists between androgen-induced changes in collagen and epithelial cell proliferation and/or differentiation in rat ventral prostate. Analyses of the temporal relationship between dihydrotestosterone (DHT)-induced changes in the synthesis and levels of collagen in the regressed ventral prostates of adult castrates demonstrated that, during the first 7 days of restoration of prostatic growth, androgen increased the synthesis as well as the degradation of collagen. Cis-hydroxyproline (CHP) treatment (2-200 mg/kg) during the first 7 days of androgen-stimulated prostatic growth, combined with maintenance of animals on a proline-free diet, produced a dose-dependent reduction in prostate weight and DNA content to a maximum of 50%. The epithelium was characterized by numerous disorganized layers of irregularly shaped and tightly packed cells, many of which had no contact with the basal lamina. There was a loss of epithelial lamina lucida and the development of a ragged lamina densa. Cis-hydroxyproline effects were reversible in that, following cessation of CHP treatment, the perturbed morphology, DNA content, and organ weight returned to the range of DHT-treated controls. Collagenous components seem to be important in supporting the normal androgen-dependent proliferation and differentiation of prostatic epithelial cells.