Dihydrotestosterone concentrations have been measured in prostatic tissue from patients with recurrent advanced prostatic cancer after 1.0 to 5.0 mg. diethylstilbestrol per day or castration with or without estrogen therapy. Although medical or surgical castration usually leads to tissue dihydrotestosterone concentrations of less than 2.4 ng./gm. 2 of 20 surgically castrated and 4 of 9 estrogen-treated patients had values above this level. The difference between the number of patients with dihydrotestosterone levels greater than 2.4 ng./gm. in the surgical castrated and estrogen-treated groups was statistically significant by a chi-square test. These differences suggest that 1) increased tissue dihydrotestosterone levels in diethylstilbestrol-treated patients may be caused by inadequate dosage or decreased compliance, and 2) increased tissue dihydrotestosterone concentrations greater than 2.4 ng./gm. in castrated patients suggest an adrenocortical androgen contribution to the prostatic dihydrotestosterone level. Therefore, patients who are castrated or treated with diethylstilbestrol should have plasma testosterone and tissue dihydrotestosterone measurements at the time of relapse. If plasma and tissue dihydrotestosterone levels are at castrate levels (plasma levels less than 0.5 ng./ml. and tissue levels less than 2.4 ng./gm.) then further hormonal therapy is not indicated. Otherwise, adrenocortical suppression should be done if plasma testosterone is at castrate levels and tissue dihydrotestosterone is elevated. When plasma testosterone is above castrate levels titration with hormonal therapy should be done while plasma testosterone is monitored to achieve plasma testosterone levels below 0.5 ng./ml.