BACKGROUND This study was designed to determine the efficacy of digital rectal examination (DRE) and serum prostate-specific antigen (PSA) for early detection of prostate cancer in men > or = 50 years of age. METHODS A prospective single-center clinical trial was conducted to screen 644 asymptomatic men, who were elicited by newspaper and radio advertisements, with DRE and PSA. Quadrant biopsy examinations of the prostate were performed if PSA > 4 ng/ml or if DRE was suspicious. RESULTS Thirty-seven percent of the men (n = 241) had an abnormality of DRE or elevated PSA. Of the 163 patients who underwent transrectal ultrasound and quadrant biopsies of the prostate, 77% had normal biopsies, 14 (8%) had prostatic intraepithelial neoplasia, and 24 (15%) had carcinoma of the prostate. PSAs ranged from 0.3 to 65.5 ng/ml, with a mean of 2.35 and a median of 1.6. Ninety-five patients had a PSA > 4 ng/ml, of whom 17 had a PSA > 10 ng/ml. Sensitivity of PSA was 75% and specificity 87%; for DRE the sensitivity was 75% and the specificity 69%. Clinical stage of patients who underwent radical prostatectomy was B1 in 15 and B2 in five. Fifteen of 20 patients (75%) had organ-confined disease; the other five had specimen-confined disease. No patient was found to have nodal involvement. CONCLUSIONS The combination of PSA and DRE seems to improve the stage of diagnosis of patients with prostate cancer. Larger, randomized studies will be necessary to evaluate the effect of screening on overall survival.