In a German multicenter trial, previously untreated patients with unresectable stages IIIA and IIIB non-small cell lung cancer were randomly assigned to receive either radiotherapy alone (arm A) or chemotherapy followed by radiotherapy (arm B). Chemotherapy in arm B consisted of ifosfamide 1,500 mg/m2 intravenously on days 1 to 5 and 29 to 33, and vindesine 3 mg/m2 intravenously on days 1 and 5 and 29 and 33. Radiotherapy started on day 1 in arm A and on day 56 in arm B. Single doses of 2 Gy were given 5 days a week for 3 weeks and after a 2-week interval for an additional 2 weeks. The total radiation dose was 50 Gy. Concurrent to radiotherapy, cisplatin was given as a radiosensitizer at a dose of 20 mg/m2 once a week. From July 1986 to March 1989, 85 patients were randomized, of whom 78 were evaluable. Main prognostic factors were well balanced. Of the patients receiving chemotherapy, 25% had a partial remission after two cycles, 46% showed no change, and 29% had progressive disease. After radiotherapy, response rates were 49% in arm A and 58% in arm B, including a 10% complete remission rate in both groups. After two thirds of the projected sample size had been included, an analysis of survival was performed and showed a statistically significant advantage for the treatment group including chemotherapy (P = .016). Median survival was 9.0 months versus 13.7 months and 2-year survival was 12% versus 24%, both in favor of the group receiving chemotherapy. These results caused premature discontinuation of patient accrual according to the study protocol and the recommendations of the Ethics Review Board of the Philipps-University Hospital. The results of this trial indicate that chemotherapy is able to prolong survival of patients with locally advanced unresectable non-small cell lung cancer and should be considered for treatment of these patients.