Prostate specific antigen (PSA), neutral serine protease secreted exclusively by prostatic epithelial cells, has a number of applications in the management of men with prostatic carcinoma. While it is widely recognized that elevated PSA correlates with the presence of carcinoma, little data exist regarding the use of PSA as the initial test in the early detection of prostatic cancer. We measured serum PSA levels in men older than 50 years and performed digital rectal examination and ultrasound guided prostate biopsy of those who had a PSA level of greater than 4.0 ng./ml. A total of 1,249 men entered the protocol, of whom 187 (15.0%) had PSA levels above 4.0 ng./ml. Digital rectal examination and ultrasound guided biopsy were performed at our facility in 105 patients (56.2%). A total of 32 carcinomas (30.5%) was detected, including 23 in men with PSA between 4.1 and 10.0 ng./ml. and 9 in men with a PSA of greater than 10.0 ng./ml. Of the 32 carcinomas 12 (37.5%) occurred in men with normal prostates or glands demonstrating only asymmetry on digital rectal examination, and 3 men had carcinoma despite normal digital rectal examination and no hypoechoic peripheral zone lesion detected on ultrasound. Of the 32 patients 30 had clinically localized carcinoma but 7 of the 16 undergoing radical prostatectomy had pathological upstaging. We conclude that PSA represents an important adjunct to digital rectal examination for the early detection of prostatic carcinoma. The efficacy of this or any other early detection test to decrease prostate cancer mortality necessitates the results of prospectively randomized clinical trials.