We evaluated the efficiency and toxicity of estramustine phosphate (ECT), ifosfamide (IFM) and cisplatin (CDDP) combination chemotherapy in twenty-one patients with hormone-refractory prostate cancer (HRPC), for which there is currently no effective treatment. Patients received a daily dose of 560 mg ECT in combination with 1.2 g/m(2) IFM on days 1 to 5 and 70 mg/m(2) CDDP on day 1. This combination therapy was given every 3 to 4 weeks. An objective response of more than 50% reduction in prostate-specific antigen was observed in 9 of 18 patients (50% and a more than 50% reduction in bi-dimensionally measurable soft-tissue lesions was observed in 2 of 7 patients (29%). The median duration of response among the cases showing partial response was 40 weeks, while the median duration of response of overall partial-response plus stable cases was 30 weeks. The median survival duration of all cases was 47 weeks. Toxicity was modest and acceptable. In conclusion, the ECT, IFM and CDDP combination chemotherapy regimen is a viable treatment option for HRPC. However, in comparison with our previous chemotherapy regimen of IFM and CDDP, no additional long-lasting effects resulting from the inclusion of ECT could be affirmed.