To assess the effect of dose escalation in the treatment of small-cell lung cancer (SCLC), 298 patients with extensive-stage disease were treated with either conventional-dose cyclophosphamide (1,000 mg/m2), doxorubicin (40 mg/m2), and vincristine (1 mg/m2), (CDCAV); or high-dose cyclophosphamide (1,200 mg/m2), doxorubicin (70 mg/m2), and vincristine (1 mg/m2) (HDCAV). No dose attenuation was allowed during the initial three cycles of therapy in either treatment arm. All patients received CDCAV in cycles 4 through 6, during which time dosages were adjusted according to granulocyte and platelet nadirs. No additional chemotherapy was administered until disease progression or relapse was documented. Complete responses were more frequent with HDCAV (22% v 12%; P = .045). However, overall response rate (63% v 53%) and median survival (29.3 v 34.7 weeks) were not significantly different (P greater than .05). HDCAV was substantially more toxic than CDCAV, causing more episodes of life-threatening leukopenia (ie, granulocytes less than 500/microL; 79% v 40%; P less than .05) and infections (15% v 4%; P less than .05). Dose intensification of cyclophosphamide and doxorubicin during induction chemotherapy did not produce any survival benefit compared with conventional dosages of these agents in SCLC patients with extensive-stage disease.