The antitumor effect of interferon inducer poly(ICLC), given prior to the radiation treatment of Lewis lung carcinoma in C57Bl mice was studied. To induce the tumors, the mice were injected subcutaneously into the hind leg with 3 X 10(4) or 3 X 10(5) tumor cells. The combination treatment consisted of poly(ICLC) given at 1.25 mg/kg 6 hours before 400 cGy of 60Co gamma rays. All treatments were given three times over 1.5 weeks. The local response, as measured by the delay in the tumor growth, was significantly higher in the combination treatment group than in poly(ICLC) or local irradiation groups. Following the termination of treatment, tumor regrowth was observed. The survival of poly(ICLC) treated mice was influenced by the number of transplanted tumor cells. Thus, untreated mice which received 3 X 10(4) or 3 X 10(5) (2 or 20 TD50) of tumor cells had similar mean survival time of 25.4 +/- 1.9 and 22 +/- 84 days, respectively (p greater than 0.05). The mice, treated by a combination of poly(ICLC) and local irradiation survived 48.2 +/- 2.1 days and 30.7 +/- 1.2 days (p less than .01), with higher survival in 2 TD50 tumor cell groups. Thus, data obtained in this study in mice showed that administration of an interferon inducer poly(ICLC) prior to local irradiation can improve tumor response and survival.