In instances of metastatic tumor from an unknown primary site, it is important to isolate those cases which are attributable to prostatic carcinoma. Immunoperoxidase localization of human prostate-specific antigen (PSA) would be useful in this regard if it were reliably detectable in prostatic carcinoma. We have studied 15 specimens from 14 patients with carcinoma of the prostate by immunoperoxidase techniques. The presence of PSA correlates with the Gleason grade. All cases of Gleason grade 9 or less demonstrated strong staining for PSA. Of the seven specimens with a Gleason grade 10, only four (57%) demonstrated significant staining, while two were entirely devoid of PSA. PSA is thus useful when it is present, but the absence of PSA in a poorly differentiated tumor of undetermined origin does not unequivocally rule out the possibility of a prostatic carcinoma.