Between 1975 and 1980, 101 patients with inoperable Stage IIIMO non-small cell lung carcinoma were entered into combined radiotherapy and chemotherapy trials at Michael Reese Hospital and University of Chicago Hospital. Sixty-four percent of the patients responded. Median survival for all patients was 8.8 months. Responders survived 13.7 months and nonresponders 4.6 months (P = 0.002). Patients treated with 4200 rad had a higher response rate than those treated with 3000 rad (74% versus 54%, P = 0.04) but there was no difference in survival. Although all patients with squamous cell carcinoma died by 30 months, 18% of patients with adenocarcinoma and 20% of patients with large cell carcinoma are long-term survivors. Brain metastases occurred more frequently in patients with large cell or adenocarcinoma than in patients with squamous cell carcinoma (P = 0.02). The prognostic effect of age, initial performance status, sex, histology, and tumor extent are examined. Toxicity was substantial with a 13% treatment-related mortality. Combined modality therapy may benefit selected patients with non-squamous cell types, but more effective chemotherapeutic agents are needed. Prophylactic cranial irradiation in patients with large cell carcinoma or adenocarcinoma may decrease the incidence of subsequent brain metastases.