Introduction: Although the biology and sites of secretion of PSA are well known, its pharmacokinetics are still unclear. This study analyzes the differences between the clearance of total and free serum PSA following open surgery for BPH and radical prostatectomy. Methods: Free and total PSA were measured in 27 patients submitted to radical prostatectomy for clinically localized prostate cancer (group I) and in 27 patients submitted to open surgery for BPH (group II). In both groups, the clearance of free and total PSA was studied. Results: Group I – the mean half-life was 1.416 ± 0.723 days for free PSA and 2.43 ± 0.688 days for total PSA. After prostate removal, free PSA showed a marked increase. Group II – the mean half-life of free PSA was 2.157 ± 1.792 days and 3.391 ± 2.337 days for total PSA. Conclusions: The increase in free PSA shortly after manipulative procedures of the prostate was higher than the increase in total PSA. Serum clearance of free PSA after eradicative prostatic surgery was related to the indication and type of procedure used.