Chemotherapy has a positive role in managing patients with stage IV non-small cell lung cancer. Randomized studies and meta-analyses comparing chemotherapy with best supportive care have confirmed a significant prolongation of survival for chemotherapy-treated patients. In recent years, several new active agents have been identified. These include the taxanes paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and docetaxel, the antimetabolite gemcitabine, the mitotic spindle inhibitor vinorelbine, and (potentially) the topoisomerase I inhibitors. Combinations of either vinorelbine or paclitaxel with cisplatin have resulted in a significant increase in median survival times compared with both cisplatin and vindesine and cisplatin and etoposide. Paclitaxel combined with either carboplatin or ifosfamide also has been promising. Since even the best current combination regimens result in median survival times of less than 1 year, the identification of more active drugs and combinations remains a high priority. One possible strategy to identify more active regimens may be the combination of three rather than two active agents into a combination regimen. Although the three-drug regimens used in the 1980s appeared to be no more active than two-drug combinations, the advent of additional active compounds with novel mechanisms of action allows this question to be readdressed. Based on this background, we have initiated a phase I/II study of carboplatin and paclitaxel with escalating doses of ifosfamide. The study design and dosing schedule are discussed in this report.