The management of hormone-refractory metastatic prostate cancer remains a therapeutic dilemma. We report the results of a phase II trial with deferoxamine administrated at a dose of 50 mg/kg (maximum dose 5 g) administered intravenously over 8 hr daily, repeated for 5 days at 4-week intervals for 2 courses. Fourteen patients with advanced hormone-refractory prostate cancer were treated and 28 courses were delivered. Essentially no toxicity was observed. Using combined clinical and prostate-specific antigen (PSA) criteria. 13 of 14 patients had disease progression. However, 9 of 14 patients had stable measurable or evaluable disease and progressed solely based on PSA criteria. Deferoxamine in this dose and schedule has no activity in hormone-refractory prostate cancer. Further investigation of the effect of deferoxamine on PSA production/expression is warranted.