We analyzed prognostic factors for non-small cell lung cancer (NSCLC) treated with hyperfractionated radiotherapy (HFX RT) with or without concurrent chemotherapy. One-hundred sixty-nine patients with histologically or cytologically proven, Stage III NSCLC, Karnofsky performance status (KPS) > or = 50, and no previous therapy were treated in a randomized trial as follows: Group 1--HFX RT to a total dose of 64.8 Gy (61 patients); Group 2--the same HFX RT with chemotherapy consisting of 100 mg of carboplatin on days 1 and 2 and 100 mg of etoposide on days 1-3 of each week during the RT course (52 patients); and Group 3--the same HFX RT with chemotherapy consisting of 200 mg of carboplatin on days 1 and 2 and 100 mg of etoposide on days 1-5 of the first, third, and fifth weeks of the RT course (56 patients). The median survival time for all 169 patients was 13 months and the 5-year survival rate was 13.4%. The median time to relapse (local or distant) was 11 months and the 5-year relapse-free survival was 12.8%. Group 2 patients had a better prognosis than Group 1 patients (P = 0.0028) but there were no differences in prognosis between Groups 2 and 3 and between Groups 1 and 3. Of potential prognostic factors examined, female gender (P = 0.00012), age > or = 60 (P = 0.00000), KPS > or = 80 (P = 0.00000), Stage IIIA (P = 0.00000), and previous weight loss < or = 5% (P = 0.00000) were associated with better prognosis. These findings were confirmed by multivariate analysis.