A Phase II randomized study testing the combination of cisplatin, etoposide, and ifosfamide (PEI) in non-small cell lung cancer (NSCLC) was performed. The standard combination of cisplatin and etoposide (PE) was used as the control arm. Since January 1987, 78 patients were enrolled and then stratified for previous treatments and performance status (PS). The response rate (RR) of PEI was 26% (95% confidence limits [95 CL], 12% to 40%), with one complete response (CR). The RR of PE was 26% (95 CL, 13% to 39%), with no CR. The median response duration was 5 months (range, 2 to 13 months) for PEI and 4 months (range, 2 to 6 months) for PE. The median survival time was 6 months (range, 1 to 22+ months) for PEI and 7 months (range, 1 to 21+ months) for PE. Leukopenia at recycling was similar in both arms (25% for PEI and 29% of PE). The median leukocyte nadir was 2100/microliters (range, 430 to 4870/microliters) for PEI patients and 3150/microliters (range, 500 to 5000/microliters) for PE patients. Three patients had a drug-related death secondary to infections. This Phase II randomized study suggested that the combination of cisplatin plus etoposide and ifosfamide produces results similar to those obtainable with cisplatin and etoposide.