The objective of this study was to evaluate the efficacy and safety of low-dose docetaxel, estramustine and dexamethasone combination chemotherapy in patients with hormone-refractory prostate cancer (HRPC). Sixty-nine patients with HRPC were enrolled. Docetaxel was given at a dose of 25 mg/m(2) on days 1 and 8 every 3 weeks, oral estramustine 280 mg twice daily on days 1 to 3 and 8 to 10, and oral dexamethasone 1 mg daily throughout the course. Cycles were repeated every 21 days. Treatment was continued until disease progression or excessive toxicity. Patients were evaluated for response and toxicity. Patients received a median of eleven cycles (range : 1-25). Prostatic-specific antigen (PSA) was decreased greater than 50% in 53 (77%) out of 69 patients and median duration of PSA response was 10.2 months. Median time to progression and overall survival 10.2 and 24 months, respectively. Grade 1-2 fatigue was the most common toxicity observed in 10 (15%) patients. Grade 3-4 toxicities were observed in five (7%) patients (2 thrombosis, 2 bilirubin elevation, and 1 aspartate transaminase/alanine transaminase elevation). Low-dose docetaxel, estramustine and dexamethasone combination chemotherapy is an effective and well tolerated treatment for Japanese HRPC patients.