Three-weekly docetaxel chemotherapy with prednisolone is now considered standard of care for patients with metastatic hormone refractory prostate cancer (MHRPC). This study reports the efficacy and toxicity of first-line docetaxel chemotherapy followed subsequently by re-treatment on biochemical disease progression (BDP). Forty-two patients with MHRPC were treated with three-weekly docetaxel chemotherapy 75 mg/m(2) and 10 mg of prednisolone daily. Median age 73 years (range 58-87) and median initial PSA 182 ng/ml (range 19.9-1500). Of these patients, 10 were re-treated with the same regimen (second-line chemotherapy) on BDP. A further 3 out of these 10 patients received 2nd re-treatment (third-line chemotherapy) with docetaxel chemotherapy on BDP. Fifty-four percent of patients responded to first-line docetaxel chemotherapy and all re-treated patients responded again with a PSA reduction >50%. Median treatment-free interval prior to second and third-line chemotherapy was 24 and 26 weeks, respectively. Grade 3 or 4 neutropenia occurred in 2.5, 7 and 12% of the total number of cycles in patients receiving first-, second- and third-line docetaxel chemotherapy, respectively. Median survival was 13 months (range 3-35) and one-year overall survival 52%. This is the first report of three-weekly docetaxel chemotherapy re-treatment in patients with MHRPC and demonstrates that patients who initially respond to docetaxel chemotherapy maintain their sensitivity to subsequent re-treatment without a significant rise in haematological toxicity.