Serum prostate-specific antigen (PSA) levels and prostate volume were evaluated in 553 healthy men aged 40 to 79 years, who entered a study program for benign prostatic hyperplasia from December 1993 to August 1994. Digital rectal examination (DRE), transrectal ultrasonography (TRUS) and serum PSA assay were performed on all participants. After excluding men with suspected prostate cancer and incomplete data, 542 cases qualified for analysis. The mean serum PSA level was 1.4 +/- 1.7 ng/mL which increased with age from 0.8 +/- 0.9 ng/mL in men aged 40 to 49 years to 2.7 +/- 2.8 ng/mL in those aged 70 to 79 years. In this study group, 250 men (46.1%) were documented to have various degrees of benign prostatic hyperplasia (BPH). The prostate volume averaged 22.3 +/- 9.1 mL which increased from 18.5 +/- 6.1 mL in the fifth decade to 27.2 +/- 13.7 mL in the eighth decade. There was a modest correlation between serum PSA level and both age and prostate volume. However, when the prostate volume was adjusted, the PSA level correlated more weakly with age in a multivariate analysis. On the other hand, the serum PSA level correlated more strongly with prostate volume when age was adjusted. Although 5.4% of the men had serum PSA levels > 4 ng/mL, there was no evidence of prostate cancer by DRE and TRUS. Serum PSA levels increased with age and prostate volume, and correlated better with the latter. These factors should be taken into account when determining the significance of a given PSA value in a patient without clinical evidence of prostate cancer.