Purpose: To investigate the efficacy of concurrent hyperfractionated radiation therapy (HFX RT) and low-dose daily chemotherapy (CHT) in stage III non-smell-cell lung cancer (NSCLC). Patients and Methods: Between January 1990 and December 1991, 131 patients with histologically or cytologically confirmed stage III NSCLC, Karnofsky performance status (KPS) greater than or equal to 50, and no previous therapy were randomly treated as follows: group I, HFX RT with 1.2 Gy twice daily to a total dose of 69.6 Gy (n = 66); and group II, same HFX RT with CHT consisting of 50 mg of carboplatin (CBDCA) and 50 mg of etoposide (VP-16) given on each RT day (n = 65). Results: Group II patients had a significantly longer survival time than group I patients, with a median survival of 22 versus 14 months and 4-year survival rates of 23% versus 9% (P = .021). The median time to local recurrence and 4-year local recurrence-free survival rate were also significantly higher in group II than in group I (25 v 20 months and 42% v 19%, respectively, P = .015). In contrast, the distant metastasis-free survival rate did not significantly differ in the two groups (P = .33). The two groups showed similar incidence of acute and late high-grade toxicity (P = .44 and .75, respectively). No treatment-related toxicity was observed. Conclusion: The combination of HFX RT and low-dose daily CBDCA plus VP-16 was tolerable and improved the survival of patients with stage III NSCLC as a result of improved local control. (C) 1996 by American Society of Clinical Oncology.