Total serum prostate-specific antigen (PSA) levels, free-to-total PSA ratio (F/T ratio) and PSA density (PSAD) were compared to clarify the clinical significance of these parameters in the diagnosis of prostate cancer (CaP) with intermediate PSA concentrations (4-10 ng/ml). PSAD and F/T ratio were obtained during the period from May 1999 to April 2001 from 43 patients with serum PSA concentrations of 4-10 ng/ml who underwent ultrasound-guided systematic sextant biopsies. PSAD was compared with total serum PSA and F/T ratio via receiver operating characteristic (ROC) curves for diagnosis of CaP. Diagnosis of CaP and non-CaP was made in 12 (27.9%) and 31 (72.1%) of the 43 patients, respectively. Mean serum PSA, PSA density and F/T ratio were 7.308 +/- 0.636 ng/ml, 0.271 +/- 0.039 ng/ml/cm3 and 16.225 +/- 4.911% in patients with CaP and 6.300 +/- 0.289 ng/ml, 0.178 +/- 0.020 ng/ml/cm3 and 15.213 +/- 0.980% in those with non-CaP, respectively. The ROC curve analysis demonstrated that PSAD predicted the biopsy outcome significantly better than F/T ratio and total PSA in all 43 patients (p < 0.05). In distinguishing CaP patients, the cutoff value of 0.16 ng/ml/cm3 for PSAD yielded a specificity level of 71.0% at a sensitivity level of 83.3%. Our study revealed that PSAD is a significant predictor in distinguishing CaP from non-CaP in Japanese men.