The therapeutic effects of irradiation, BCNU, or combined irradiation and BCNU were studied in the avian sarrcoma virus (ASV)-induced glioma model in rats. Whole-head orthovoltage radiation therapy was given in six equal fractions over 2 weeks, and BCNU was administered intraperitoneally as a single dose of 10 mg/kg. Two series of experiments were performed in order to duplicate the results. In Series I, the median survival times of the experimental groups, in days after randomization were as follows: control group (no treatment), 69; group receiving 200 rads, 84 (p less than 0.05); group receiving BCNU, 80.5 (p less than 0.1); and group receiving 2000 rads + BCNU, 112 (p less than 0.001). In Series 2, the median survival times were: control group, 73.5; group receiving 2300 rads, 85 (p less than 0.01); group receiving BCNU, 92.5 (p less than 0.025); and group receiving 2300 rads + BCNU, 123.5 (p less than 0.001). In both series, combined therapy was significantly better than either radiation or BCNU alone. This is the first time that a synergistic effect of BCNU and irradiation has been reported in an in vivo brain-tumor model and supports the clinical use of this combination in the treatment of malignant gliomas.