As a continuation of a previous controlled trial using "high-dose" metronidazole as a specific sensitizer of hypoxic cells, we used a more efficient nitroimidazole derivative (misonidazole, MISO) in combination with higher doses of radiation in patients with supratentorial high-grade astrocytomas. Sixty-six patients were stratified according to functional level and histological grading, and randomly allocated within 2 weeks of operation of 1 of 3 therapeutic groups: 1, conventional radiation alone; 2, large fractions of radiation with high-dose metronidazole; and 3, radiation as in Group 2 but with equitoxic doses of MISO. We examined survival as the principal end-point of the study. Neither by increasing the dose of radiation over the previous study, nor by using a more efficient sensitizer, were we able to improve survival over the current conventional daily fractionated radiation.