We studied 103 patients seen in our Prostate Cancer Detection Clinic to determine whether a correlation exists between serum prostate-specific antigen (PSA) values and ultrasound-calculated prostate gland volume. Seventy men (68%) had a PSA value less than or equal to 4 ng/ml (our upper limit of normal). The men were subclassified by prostate gland volume at arbitrary break points. Twenty-five men (24%) had a prostate gland volume less than or equal to 25 cm3; in 96%, the PSA value was less than or equal to 4 mg/ml. Further analysis revealed that the percentage of men with a normal serum PSA value decreased as the prostate gland volume increased; 65.6% of the group with a gland volume between 25 and 50 cm3 (40 of 61) and 35.5% of the group whose prostate volume exceeded 50 cm3 (6 of 17) had PSA values less than or equal to 4 ng/ml. Four men had PSA values greater than 20 ng/ml; all had prostate cancer. Cancer was diagnosed in four additional patients, three with PSA values between 5 and 10 ng/ml and one with a PSA value less than 4 ng/ml. There appears to be a direct relationship between prostate gland volume and PSA value, as well as a cancer value threshold. The clinical implications of these findings are discussed.