Ninety previously untreated patients with histologically documented lung cancer were treated with VP-16 and cyclophosphamide either alone (protocol I) or with methotrexate (protocol II) or Adriamycin (protocol III), with 30 patients in each protocol. The rates of objective response were 57,37, and 27%, respectively, protocol I being significantly better than protocol III (P less than 0.05). Protocol I was significantly less toxic than protocols II(P less than 0.01) and III (P less than 0.001). The overall rate of objective responses was 66% in small cell (SCC) and 22% in non-small cell carcinoma (nSCC). Median survival was 37 weeks in SCC and 21 weeks in nSCC. Median survival of responders both in SCC and in nSCC was significantly longer than in nonresponders. We conclude that VP-16 plus cyclophosphamide is a well tolerated regimen with positive effect in advanced lung cancer. The association of methotrexate or Adriamycin didn't offer any improvement over the basic combination in this study.