Fifty five patients with small cell lung cancer with treated with VP16-213 combination chemotherapy regimen in two consecutive series. The first series included 24 patients; 10 with limited and 14 with extensive disease were treated with VP16-213, 120 mg/m2 p.o. daily for 5 consecutive days, Cyclophosphamide 600 mg/m2 i.v. and Cisplatin 80 mg/m2 i.v. with hydratation and manitol induced diuresis. The cycle was repeated every 3 weeks. The second series included 31 similar patients, 16 limited, and 15 extensive disease, treated with VP16-213 at the same dose and Cyclophosphamide at 1,200 mg/m2 i.v. also repeated every 3 weeks; after three cycles the patients were treated with radiotherapy to the primary tumor and regional lymph nodes with 4,000 rads in a split course of three weeks interval, followed by the same combination chemotherapy. Response rate was 75% for the first series with 6 of 24 (25%) of complete responses in four limited and two extensive disease and a median survival time of 24 weeks. In the second series of patients there were 26 of 31 (83.8%) responses with 10 of 31 (32%) complete responses in nine limited and one extensive disease and a median survival time of 33 weeks for responders. Duration of response for complete responders was 36.8 weeks for the first series and 51 weeks for the second. Toxicity was mild and includes nausea and vomiting, myelosupression, alopecia in both series, with one toxic death in the second series. Both regimens are active with a low complete response rate, which was increased in the second series by the addition of radiotherapy, which did not increase overall survival.