This paper presents a review of the progressive clinical trials of the hypoxic cell radiosensitizer, misonidazole, in the Radiation Therapy Oncology Group (RTOG). Presentation is made of all the schemas of the recently completed and currently active RTOG Phase II and Phase III studies. Detailed information is provided on the clinical toxicity of the Phase II trials, specifically regarding neurotoxicity. With limitations in drug total dose, a variety of dose schedules have proven to be tolerable, with a moderate incidence of nausea and vomiting and mild peripheral neuropathy, and a low incidence of more severe peripheral neuropathy or central neuropathy. No other organ toxicity has been seen, specifically no liver, renal or bone marrow toxicities. The clinical pharmacologic monitoring of misonidazole blood levels has been satisfactory with good correlation between the group-wide (Phase II) UV values and the HPLC values from the Phase I study. The patient accrual of the trials has been rapidly increasing and an early analysis suggests efficacy better than previous radiation experience. A series of eight Phase III trials are currently underway or proposed in the RTOG and the results of these are pending. An additional Phase III malignant glioma trial in the Brain tumor Study Group is described.