Vinorelbine-cisplatin combination chemotherapy is a standard approach for the treatment of advanced non-small-cell lung cancer (NSCLC). The addition of paclitaxel as a third therapeutic agent seems promising. The aim of the present study was to evaluate the activity and toxicity of this new regimen. Forty-six nonselected and chemotherapy-naive patients with stage IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 2 were treated every 4 weeks with paclitaxel (135 mg/m2 given iv in 3 hours) and cisplatin (120 mg/m2 given iv in 6 hours) on day 1 and vinorelbine (30 mg/m2 given iv in 30 minutes) on days 1 and 15. All patients were evaluated for toxicity and response according to the intent-to-treat principle. An objective response was observed in 39% of the patients (95% CI: 25% to 55%). World Health Organization grade III to IV neutropenia, thrombocytopenia, and anemia occurred in 43%, 2%, and 17%, respectively. There was one treatment-related death. Nonhematologic toxicities were mild, mainly grade III nausea and vomiting in 20% of the patients. After a median follow-up period of 54 months, the median progression-free survival was 14.3 weeks and the median overall survival was 31.3 weeks. This three-drug chemotherapy combination is feasible, well tolerated, and shows activity in metastatic NSCLC.