The activity and distribution of five hydrolytic enzymes in human prostatic carcinomatous tissue were studied before and during treatment with estramustine phosphate, Estracyt, in 13 patients with prostatic carcinoma, stage IV. Seven of the patients had, and 6 had not, received other treatment before the trial. In the previously untreated patients estramustine phosphate induced enzymatic changes similar to those known to be produced by conventional estrogen therapy. Histochemically, estramustine phosphate therapy—in contrast to estrogen therapy—produced an increase in lipofuscin in the biopsy specimens studied, an observation possibly suggesting a cytostatic or cytotoxic effect of the drug. In the previously estrogen-treated patients estramustine phosphate caused some enzymatic changes indicating that the compound has some effect over and above that of the previous treatment.