A limited clinical trial of Interferon-beta (Human Fibroblast Interferon) in the treatment of advanced, hormone-refractory prostate cancer was conducted by the National Prostate Cancer Project (NPCP Protocol 2100). Sixteen patients with metastatic prostate cancer who had failed prior hormone therapy were entered into the study. Treatment consisted of 6 X 10(6) units of Interferon-beta intravenously three times per week for 12 weeks. Chills and fever were seen in ten of the 16 patients (62.5%), and mild hematologic toxicity occurred in four patients. No complete or partial responses were observed. Three patients had stable disease by NPCP criteria for a mean duration of 6.3 months. Progression of disease was seen in 13 of the 16 patients, eight of whom progressed during therapy. The results of this study suggest that Interferon-beta has limited efficacy in the treatment of advanced, hormone-refractory prostate cancer.