The concentration of a novel 65 kDa oncofetal protein, p65, was measured in the sera of patients with prostatic malignancies using an enzyme-linked immunosorbent assay. The prostate cancer sera were positive for p65 in 40 out of 59 cases (68%), while only 7 of 79 normal sera (9%) and 12 of 61 sera from patients with benign diseases (20%) were positive. The detection system had an overall sensitivity of 68% and a specificity of 86%. Elevated p65 levels correlated positively with the pathologic stages of the prostate cancer. Using this marker in concert with PSA may increase our ability to evaluate treatment response and aid in early detection of prostate cancer.