BACKGROUND. The total prostate-specific antigen (t-PSA) in serum measured by PSA assays represents the sum of free (f-PSA) and PSA complexed with alpha 1-antichymotrypsin. The f-PSA/t-PSA (F/T) ratio in prostate cancer (PCA) patients is lower than in patients suffering from benign prostatic hyperplasia (BPH). This review summarizes the currrent literature on the clinical relevance of measurement of the F/T PSA ratio. METHODS. Discussed are: physiology of PSA, assays for t-PSA and FIT ratio, factors which bias the F/T PSA ratio, use of F/T PSA ratio in the detection of PCA, correlation with histological features, and pathological stage. RESULTS. Using the F/T ratio in the intermediate t-PSA range, a reduction of approximately 30% in biopsies can be accomplished in the detection of prostate cancer. CONCLUSIONS. The F/T PSA ratio could become a valuable tool in the differentiation of BPH from PCA. To accomplish this goal, an international standardization not only for the t-PSA measurement but also for the F/T PSA ratio must be a priority for manufacturers of PSA assays. (C) 1996 Wiley-Liss, Inc.