OBJECTIVE To evaluate the combination of vinorelbine, ifosfamide and cisplatin (VIP) in patients with advanced non-small-cell lung cancer (NSCLC). METHODS Seventy-six untreated patients with stages IIIB-IV NSCLC; the chemotherapy regimen consisted of vinorelbine (25 mg/sqm on days 1 and 8), ifosfamide (3 g/sqm on day 1 with uroprotective mesna), and cisplatin (80 mg/sqm on day 1). The cycles were administered on an outpatient basis every 3 weeks. RESULTS Leukopenia was the most frequent toxicity: grades 3-4 neutropenia was observed in 26% of the cycles and 19 episodes of febrile neutropenia were reported in 289 evaluable courses. Filgrastim 5 micrograms/kg was administered in 27% of the courses. Sixty-seven of 76 patients were evaluable for response: the overall response rate was 51% (95% confidence interval 35%-77%) with 2 complete responses (3%) and 32 (48%) partial responses. No significant differences in response rate were observed according to histology or stage of disease. The median time to progression was 6 months (range 1 to 29+) and the median overall survival 10 months (range 1-33+). CONCLUSIONS The combination of vinorelbine, ifosfamide and cisplatin in the dose and schedule employed in this trial shows an interesting response rate with acceptable toxicities. This regimen should be tested in the multimodality therapy of stage IIIA/B NSCLC.