A sensitive technique using reverse transcription and polymerase chain reaction (RT-PCR) has been used to detect circulating tumor cells in the peripheral blood of men with prostate cancer. We evaluated the clinical utility of this method for staging and monitoring for prostate cancer. Peripheral blood from 39 patients with prostate cancer and 7 non-prostate cancer controls was analyzed for prostate specific antigen (PSA) messenger RNA (mRNA) using RT-PCR. In 8 among 22 patients (36.4%) with clinically localized prostate cancer (T2 or T3), PSA mRNA was detected by RT-PCR (RT-PCR positive). Five out of 8 patients (62.5%) with regional lymph node and/or bone metastases were RT-PCR positive. The number of patients with RT-PCR positive was more frequent in a higher clinical stage. In 22 patients with clinically localized prostate cancer, 2 of the 9 patients who underwent radical prostatectomy had positive surgical margins and both patients were RT-PCR positive. Six of the 7 patients with negative surgical margin were RT-PCR negative. In the 9 cases that had been treated by combined antiandrogen blockade for metastatic prostate cancer, 4 patients whose serum PSA level were less than 4 ng/ml were all RT-PCR negative. More over 4 of 5 patients with more than 4 ng/ml of serum PSA level were RT-PCR positive. All control samples were RT-PCR negative. This study suggested that this technique using RT-PCR may provide useful information in treating patients with prostate cancer, especially for candidates for radical prostatectomy. The value of this modality as a prognostic factor awaits for further follow-up.