Racial differences in serum prostate specific antigen (PSA) values in men with and without prostate cancer have been observed but have yet to be explained. We aimed to determine if ethnic variations in the rate of metabolism of PSA could explain the different levels of PSA found in African-American and Caucasian men. In a prospective fashion, patients diagnosed with biopsy-proven clinically localized adenocarcinoma of the prostate and scheduled for radical prostatectomy were selected for the study. Eleven patients (six Caucasian, five African-American) were enrolled in the study. All patients demonstrated normal liver and renal function. Sera for total PSA were obtained at the following time intervals: preoperative (within 3 months of operation), time 0 (at time of prostate removal), 1, 4, 8, 24, 48, 72, 168 and 336 h after removal of the prostate. A log-linear regression model was then used to determine the metabolic clearance rate and half-life of serum total PSA. There were no statistically significant differences between Caucasian and African-American patients with regard to age, PSA prior to surgery, prostate weight, Gleason sum and PSA half-life. The metabolic clearance of total PSA followed first order kinetics. When comparing serum PSA levels expressed as a fraction of the baseline PSA, Caucasian and African-American patients demonstrated similar rates of metabolism. This study found similar rates of elimination of serum total PSA between African-Americans and Caucasians. These findings suggest that the rate of metabolism of PSA is similar for these groups. Further studies are needed to explain racial differences of serum PSA in patients with and without prostate cancer.