Immunoperoxidase staining for prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) help to identify patients with prostatic carcinoma presenting as metastatic disease from an occult primary source. To clarify further the reliability of these prostatic tissue antigens, we have examined the primary tumor and metastatic sites in 16 autopsy cases. Eleven of these had diffusely positive findings for PSA and PAP in the primary and all metastatic sites, and 1 case lacked both antigens in all locations. Four cases demonstrated variability between these antigens and among various sites. Prostatic primary lesions contained PAP and PSA in 13 (81%) and 12 (75%) cases, respectively. The most reliable metastatic sites were lymph nodes, seminal vesicles, lung, bone, and kidney; while liver, adrenal, and colorectal sites were less reliable. No relationship existed between serum PAP levels and tissue detectability of PAP. The use of both PAP and PSA increases the likelihood of properly identifying the prostate as the organ of origin of metastatic disease. In spite of the use of both markers, however, three primary lesions would have been misdiagnosed, and 1 case lacked both antigens in all metastatic sites as well. In poorly differentiated lesions, the lack of both antigens does not unequivocally eliminate the possibility of prostatic carcinoma.