Between 1975 and 1979, 271 patients with regional small cell undifferentiated (including oat cell) carcinoma of the lung were entered into a study involving treatment by radiation therapy (4500 cGy (rad) in five weeks) to the primary tumor, mediastinum and supraclavicular lymph nodes, and a randomization to receive or not receive prophylactic treatment of the brain (3000 cGy in two weeks) and a randomization to prophylactic or delayed chemotherapy (cyclophosphamide and CCNU). Analysis of the data indicates that the median survival for responders (53 weeks) was significantly longer than that of the non-responders and partial responders (37 and 34 weeks). Median survival by treatment arm was 48 weeks for thoracic irradiation (TI), brain irradiation (BI), and early chemotherapy (CT), 44 weeks for TI alone, 41 weeks for TI and CT, 38 weeks for TI and BI. Regional complete and partial tumor responses were 52 and 25% for prophylactic chemotherapy and 44 and 35% for delayed chemotherapy. The site of first failure was regional in 12%, regional and distant simultaneously in 21%, and distant only in 46%. Elective brain irradiation significantly reduced the incidence of brain metastases from 21 and 5%, but did not improve survival.