Twenty-five patients with advanced non-small-cell lung carcinoma (NSCLC) were treated with a multidrug regimen (CIV) consisting of ifosfamide (IFX), cisplatin (CDDP), and etoposide (VP-16). Twenty-four patients were evaluable for response. An objective response was detected in eight cases (33%), including one case with complete tumor response. Median duration of response was 31 weeks, and median overall survival 46 weeks, with no significant difference between responders and nonresponders. Myelosuppression and gastrointestinal side effects represented the main toxic manifestations; a toxic death and an ischemic cardiac episode were also observed. CIV seems a moderately effective regimen in NSCLC, but unlikely to provide an advantage over the widely employed two-drug combination of CDDP and VP-16.