Seventeen ambulatory patients with extensive-stage small-cell lung cancer received one or two courses of high-dose induction chemotherapy consisting of cyclophosphamide (100 mg/kg) plus etopside (1,200 mg/m2) followed by four or five cycles of conventional-dose cyclophosphamide (1,000 mg/m2), doxorubicin (40 mg/m2), and vincristine (1.4 mg/m2) (CAV) given every 21 days. No additional chemotherapy was given until relapse or progression was documented. Response was assessed initially after high-dose induction therapy and again after completion of all chemotherapy. After induction therapy, 16/17 (94%) patients had achieved an objective response, including five (29%) complete responses and 11 (65%) partial responses. Two partially responding patients improved to a complete response after CAV, while one partial responder progressed and one patient died of an intercurrent illness while receiving CAV. Thus, the overall response after completing all chemotherapy was 15/16 (94%), including seven (44%) complete responses and eight (50%) partial responses. Median response duration was six months (range, 3 to 11 months), and overall median survival was ten months (range, 2 to 17 months). All 31 courses of induction therapy were associated with leukopenia (less than 1,000/microL), 81% with thrombocytopenia (less than 20,000/microL), and 77% with fever (greater than 38.5 degrees C). Seven episodes of bacteremia and one axillary abscess were documented, and there was one treatment-related death (6%). These toxicities are similar to that produced by high-dose etoposide alone. High-dose cyclophosphamide combined with high-dose etoposide can be administered to ambulatory patients with extensive-stage small-cell lung cancer without requiring bone marrow transplantation to reestablish hematopoiesis. Complete response and median survival rates, however, are similar to those obtained with less intensive therapy.