The radiation therapy oncology group conducted a phase I/II trial of hemibody irradiation combined with high-dose misonidazole in the management of metastatic solid tumors. Thirty-seven patients received 39 hemibody irradiation treatments, each preceded by 4 g/m2 or 5 g/m2 misonidazole orally. One fraction of 600 cGy was delivered to a half-body volume. Objective tumor response occurred in 21% of evaluable patients, including one complete response. Pain relief was documented in only 36%. Acute toxicity consisting of nausea and vomiting was significant; 54% of patients experienced severe or very severe reactions. Other toxicities were acceptable. The low response rate and high acute toxicity contraindicate the use of misonidazole with hemibody irradiation for palliation.