Objectives. To assess the relationship of the distribution of serum prostate-specific antigen (PSA) to age in a population of subjects for whom PSA levels were determined as part of a health fair, Methods. Between March 19 and March 28, 1993, 1716 men aged 40 to 79 years from eastern Nebraska who participated in ''The Health Fair of the Midlands'' provided blood for serum PSA determination, Results, Serum PSA concentration was correlated with patient age, with the observed 95th percentile increasing from 1.5 ng/mL for subjects 40 to 44 years of age to 7.7 ng/mL for subjects 75 to 79 years of age. Variability in serum PSA concentrations increased with increasing age, Taking this heteroscedasticity into account provided the following upper limits of normal (95th percentiles) for serum PSA: age 40 to 49, 1.5; age 50 to 59, 2.6; age 60 to 69, 4.4; age 70 to 79, 7.5. Conclusions. Previously published age-specific reference ranges did not consider the increasing variability of PSA concentration with age and have upper limits of normal that are too high for subjects under age 60 and may be too low for subjects aged 70 to 79. Upper reference ranges of 1.5 ng/mL for subjects aged 40 to 49, 2.5 ng/mL for subjects aged 50 to 59, 4.5 ng/mL for subjects aged 60 to 69, and 7.5 ng/mL for subjects aged 70 to 79 years provide specificity near 95%.