The objective of the present study was to evaluate the activity and the toxicity of an original combination of paclitaxel (Taxol), ifosfamide, and carboplatin in patients with stage IIIB-IV non-small-cell lung cancer (NSCLC). Sixty-one patients with previously untreated stage IIIB-IV NSCLC were enrolled by five institutions. Paclitaxel was given at the dose of 200 mg/m iv in 3 hours, ifosfamide (with mesna) at the dose of 3 g/m and carboplatin at an area under the curve 5, on day 1, every 21 days for a total of six cycles in responding or stabilized patients. Among the 59 patients evaluable for response, 2 complete remissions and 25 partial remissions were achieved for an overall response rate of 45.7% (95% CI = 32.7-59.2). According to an intention-to-treat analysis, the response rate was 44.2%. Thirteen patients had a stable disease, whereas 19 progressed. The median time to progression was 7.7 months (range: 1-18), whereas the median overall survival was 10 months (range: 1-30+). The 1-year survival rate was 43%. Hematologic toxicity was exceptionally mild, and peripheral neurologic toxicity of grade III was experienced by only three patients. There was one toxic death. This original triplet regimen based on paclitaxel, ifosfamide, and carboplatin has proved active, safe, and easy to deliver on an outpatient basis for patients with advanced NSCLC. Randomized studies both versus carboplatin-paclitaxel and other triplets are clearly warranted.