We have compared the concentrations in serum of gamma-seminoprotein (gamma-SM) and prostate specific antigen (PSA), two antigens of prostatic origin that are synthesized independently of prostatic acid phosphatase (PAP, EC 3.1.3.2), to assess their potential in monitoring prostatic cancer. At presentation, 27/30 (90%) patients with metastases had a PSA concentration greater than 10 ng/mL, and 29/30 (97%) a gamma-SM concentration greater than 10 ng/mL; 21/61 (34%) with disease but without metastases had an abnormal content of PSA, and 23/61 (38%) an abnormal gamma-SM. Concentrations of PSA and gamma-SM were significantly correlated (r = 0.68, p less than 0.001). In 20 patients without metastases followed longitudinally, the median concentrations of gamma-SM, PSA, and PAP in the 13 patients who developed bony metastases or showed signs of local spreading of the tumor were 58 ng/mL, 34 ng/mL, and 2.1 U/L, respectively. The corresponding median values in the seven patients who remained clinically stable were 2.5 and 3.9 ng/mL, and 2.3 U/L. We conclude that either PSA or gamma-SM can warn of disease progression when PAP activities are still within normal limits.