We performed a clinical evaluation of Misonidazole (MISO) radiosensitization in brachytherapy and two schedules of hypofractionated external radiotherapy in 3 non randomized studies. MISO (1 g/m2/d) was administered to patients with ENT tumors treated by brachytherapy, two applications of 35 Gy each with an interval of 1 month. For 46 patients with tumor responses less than 50% (in the largest dimension) at time of second application, 21 received MISO and 25 did not. For these poorly radiosensitive tumors, the addition of MISO significantly increased the rate of complete remission from 9/25 (36%) in controls to 14/21 (67%) (p less than 0.05). We studied MISO with radiation hypofractionation for conservative breast cancer with 4 fractions over 17 days (5 Gy on days 1, 3 and 6.5 Gy on days 15 and 17). Brachytherapy alone was delivered three weeks later. MISO (1 g/m2/d) was given to 38 patients with 87 acting as controls. Radiosensitization was measured by mean tumor diameter at brachytherapy, which showed a residual mass of 33% in the group without MISO and only 17% in the group with MISO (p less than 0.05). We also studied MISO with radiation hypofractionation for large ENT tumors with 14 fractions over 45 days, 2 sessions with a 4 hour interval per day for totals of 6 Gy on days 1 and 3; 8 Gy on days 15, 17, 29, 31; and 6 Gy on day 45. MISO (1 g/m2/d) was given to 49 patients with 21 acting as controls. MISO increased the rate of complete remission from 7/21 (33%) in controls to 32/49 (65%) (p less than 0.02).