To study significance and limitations of the ratio of free to total prostate specific antigen (f/t PSA) in differential diagnosis between prostate cancer and benign prostatehyperplasia (BPH) with total PSA (tPSA) levels between 4 and 10 ng/ml.We analysed retrospectively 180 prostate cancer and BPH patients who were diagnosed and treated in our hospital from October 1998 to October 2002 and had serum tPSA levels between 4 and 10 ng/ml. Of the 180 patients, 36 (20%) were histologically confirmed as prostate cancer and 144 (80%) BPH. The tPSA and free PSA (fPSA) in serum were measured by micropartical enzyme immunoassay. Prostate volume was measured by transabdominal ultrasonography. We chose Student's t-test for comparison between prostate cancer and BPH groups. The correlation between prostate volume and f/t PSA was analyzed using Pearson's correlation coefficient.The mean values of tPSA and f/t PSA were 6.75 ng/ml and 0.17 in patients with prostate cancer, 6.48 ng/ml and 0.25 in patients with BPH. The mean value of tPSA wasn't significantly different between patients with prostate cancer and BPH (P > 0.05). However, the mean value of f/t PSA of patients with prostate cancer was significantly lower than that of patients with BPH (P 0.05).The f/t PSA is significant in differential diagnosis between prostate cancer and BPH with tPSA levels between 4 and 10 ng/ml. But prostate volume has an effect on f/tPSA. The f/tPSA has diagnostic value of differentiation only when the prostate volume is less than 40 cm(3).