Twenty previously untreated patients with histologically or cytologically proven non-small cell lung cancer (NSCLC) were treated with ifosfamide in combination with cisplatin and etoposide. Patients received ifosfamide 4 g/m2 with mesna uroprotection on day 1 and cisplatin 25 mg/m2 and etoposide 100 mg/m2 on days 1 through 3. Courses were repeated every 28 days. Premedication with prochlorperazine, dexamethasone, and high-dose metoclopramide was given to prevent nausea, and lorazepam was added on days 2 and 3 only. Seventeen male and three female patients (median age, 57 years) have been treated. Two patients had stage IIIb disease, and 18 had hematogenous metastases. Eighteen patients are evaluable for response and toxicity, and it is too early to evaluate two patients. Early in the study, two patients died of toxicity and have been classified as nonresponders. One patient achieved complete response (21+ weeks), and seven patients achieved partial response (median, 30+ weeks; range, 5 to 38+), for an overall response rate of 44.5%. The median survival of the group has not been reached, and 14 patients are alive 5 to 38+ weeks from the start of treatment. The median nadir granulocyte count was 0.275 x 10(9)/L (range, 0 to 2.283 x 10(9)/L), and there were six episodes (involving 5 patients) of neutropenia-associated fever, one of which resulted in death. The median nadir platelet count was 120 x 10(9)/L (range, 13 to 385 x 10(9)/L), but no patient experienced bleeding or required platelet transfusions. Five patients required RBC transfusions. Only eight patients had grade 2 gastrointestinal toxicity, and one patient had microscopic hematuria; there was no CNS toxicity.