Study Objective: To determine the effect of concurrent chest radiation therapy on response rate, recurrence, and treatment toxicity among patients with limited stage small cell lung cancer who are receiving combination chemotherapy. Design: Randomized trial with a median follow-up of 57 months. Setting: A single government institution--the National Cancer Institute. Patients: Consecutive sample of 96 patients with histologically confirmed small cell lung cancer that was confined to the hemithorax of origin or mediastinal and supraclavicular nodes, and which could be encompassed within a tolerable radiation portal ("limited stage"). All patients were followed until death or the end of the study period. Interventions: Chemotherapy: Cyclophosphamide, methotrexate, and lomustine in 6-week cycles alternating with vincristine, adriamycin, and procarbazine in 6-week cycles, for a total of 48 weeks. Radiation therapy: Chest irradiation to 40 Gy in 15 fractions over 3 weeks, given simultaneously with the first chemotherapy cycle. Measurements and Main Results: The combined therapy led to a significantly higher response rate (complete responses, 81%, compared with partial responses, 43%; 95% Cl for the difference, 20% to 56%), significantly improved local control of the chest tumor (p less than 0.001), and significantly longer survival (p less than 0.035) (median, 15.0 months, compared with 11.6 for chemotherapy alone). The combined therapy produced significantly more myelosuppression, weight loss, esophagitis, and pulmonary dysfunction. There were more infections and deaths from toxicity in the combined treatment group, but the differences between groups were not statistically significant. Conclusion: A regimen of combined chemotherapy and chest radiation therapy given concurrently is superior to chemotherapy given alone in inducing remission and prolonging survival in patients with limited stage small cell lung cancer, and the benefit of combined therapy is reduced by its greater toxicity.