Thirty-eight patients with small cell carcinoma and no prior therapy were treated with a combination chemotherapy program including 60 mg/m2 of cis-dichlorodiammineplatinum(II) (cis-platinum) iv on Days 1 and 22 and 120 mg/m2 of VP-16-213 iv on Days 4, 6, 8, 25, 27, and 29. This was followed by 1000 mg/m2 of cyclophosphamide, 40 mg/m2 of Adriamycin, and 1.4 mg/m2 of vincristine, all given iv on Days 42, 63, 84, and 105. The program was then recycled, with cis-platinum and VP-16-213 beginning on Day 126 and the regimen repeated as above. All patients received prophylactic whole-brain radiation (usually at a dose of 3000 rads in ten fractions) between Days 42 and 63. The projected duration of treatment is 18 months in the absence of relapse. In 21 patients with limited disease, the complete response rate was 52% (5.75+--15.25+ months) and the partial remission rate was 48% (2.25--10.5 months). The extensive-disease group showed a complete remission rate of 41% (4.75--11+ months) and a partial remission rate of 47% (3.75--11.5+ months). Response to therapy with cis-platinum and VP-16-213 was very rapid and invariably maximal by the end of the 6-week induction period. Survival for the limited-disease group appears encouraging but followup time is insufficient. Toxicity included nausea and vomiting, myelosuppression, alopecia, and renal insufficiency which was dose-limiting in two patients. The cis-platinum and VP-16-213 combination is clearly an active induction regimen in small cell carcinoma of the lung, but whether it will play a role in increasing long-term survival rates remains to be seen.