Twenty-three patients with marginally resectable and unresectable non-small-cell lung cancer (stages IIIA and IIIB) were treated by neoadjuvant chemotherapy. All patients received three cycles of preoperative chemotherapy with two alkylating agents, cyclophosphamide 2.5 g/m2 intravenously (i.v.) and ifosfamide 3.5 g/m2 i.v., mesna 12 g/m2 was given additionally to prevent drug hematuria. Six of 23 patients (26%) had partial response. Of the seven patients who underwent thoracotomy, two were completely resected, but with macroscopic residual disease. Mean time to progression for the whole group was 7 months. Fifteen patients had progression of disease, with local metastases only in six, and distant metastases in eight. After administering 52 chemotherapy cycles, cyclophosphamide-ifosfamide doses were cut down, as eight of 16 patients required hospitalization for fever during neutropenia nadirs. This two-alkylating (non-cisplatin) regimen, unlike cisplatin-based regimens, was ineffective, and further trials are not recommended.