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Purpose: We examined the usefulness of measurements of free prostate specific antigen (PSA) and PSA density for predicting prostate cancer in men who had had a prior negative biopsy, a serum PSA level of 4.1 to 10.0 ng./ml. and benign findings on prostate examination., Materials and Methods: We measured percent free serum PSA and PSA density in 163 male volunteers age 50 years or older who were advised to have repeat prostatic biopsies for a serum PSA level of 4.1 to 10.0 ng./ml., Results: Of 99 men who had repeat biopsies 20 (20%) had prostate cancer detected. Prostate cancer was significantly associated with lower free PSA level and higher PSA density, with overlap in 83% of the cases. The use of percent free PSA cutoffs of 28 and 30% would have detected 90 and 95% of cancers, respectively, and avoided 13 and 12% of the biopsies, respectively. PSA density cutoffs of 0.10 and 0.08 would have detected 90 and 95% of cancers, respectively, and avoided 31 and 12% of biopsies, respectively., Conclusions: Free PSA and PSA density predict prostate cancer in men who have had prior negative prostatic biopsies, serum PSA levels of 4.1 to 10.0 ng./ml. and a benign prostate examination. Both parameters may be used to avoid unnecessary biopsies with an acceptable decrease in sensitivity. Further studies are needed to determine cutoffs to be used in clinical practice.