We have evaluated the combination of ifosfamide, carboplatin, and etoposide (ICE) along with mesna in 46 patients with stage IV non-small cell lung cancer. Treatment consisted of ifosfamide (1.25 g/m2/d with mesna) and etoposide (80 mg/m2/d) given intravenously on days 1 to 3 and carboplatin (300 mg/m2) given intravenously on day 1 every 4 weeks. Eligibility criteria included measurable disease; adequate hematologic, hepatic, and renal functions; no prior chemotherapy; and an Eastern Cooperative Oncology Group performance status (PS) of 0 to 3. Two patients were lost to follow-up and one had received prior chemotherapy, leaving 43 patients evaluable for response and toxicities. There were 27 male and 16 female patients. Twenty-three patients had a PS of 0 or 1 and 20 had a PS of 2 or 3. Eighteen patients had received prior radiotherapy. There were two complete responses and nine partial responses. The response rate was 35% in PS 0 or 1 patients and 15% in PS 2 or 3 patients. The most frequent toxicity was myelosuppression; 44% of patients experienced grade 3 or 4 leukopenia and 14%, grade 3 or 4 thrombocytopenia. Patients receiving prior radiation were significantly more prone to develop leukopenia (P = .01). Five patients developed leukopenic fever, and three died of sepsis. Gastrointestinal toxicities were mostly mild. No neurologic or genitourinary toxicities were observed. The median length of survival was 209 days for patients with a PS of 0 or 1 and 123 days for the entire group. The 1-year survival rate was 22% and 19%, respectively, in these two patient subgroups. ICE is an active regimen in patients with metastatic non-small cell lung cancer and a good PS. Myelosuppression is the major dose-limiting toxicity. Hematopoietic growth factors may be indicated in subsequent studies, especially in patients who had prior radiation therapy. The therapeutic effect of ICE on patients with a poor PS remains unsatisfactory and requires further investigation.