One hundred eleven patients with inoperable but limited-stage small cell lung cancer were treated with three courses of cyclophosphamide (1.5, 2.5, and 3.5 g/m2, respectively) and VP-16-213 followed by methotrexate and thoracic radiotherapy. The total duration of treatment was 3 months. Patients were included who had pleural effusions, contralateral neck nodes, and bone marrow infiltration. The complete response (CR) rate was 56%, the majority confirmed by repeat bronchoscopy, with an 81% overall response rate. The minimum follow-up was 14 months. Median survival for all 111 patients was 11 months and 14 months (1-34+) for complete responders; the median survival was also 11 months for the 91 patients with conventional limited-stage disease, although 15 of the 19 patients alive at 14 months or more were from this subpopulation. There was no significant difference in the survival of those CR patients whose response was confirmed bronchoscopically and patients whose CR was assessed only radiologically and clinically. Forty-four patients with leukopenia (less than 1000 cells/microliter) received intravenous antibiotics for malaise and suspected infection. Close monitoring between treatments and direct access of patients to the hospital was encouraged. The majority of patients improved symptomatically as assessed by Karnofsky and Respiratory scores. These results support the view that short but intensive treatment without long-term or maintenance chemotherapy is beneficial.