From March 1993 to February 1997, 43 eligible patients with inoperable stage IIIA (ten patients) and stage IIIB (33 patients), histologically confirmed NSCLC received 3 courses of the ICE combination (ifosfamide 1.5 g m(-2) and mesna 750 mg m(-2) two times a day, cisplatin 25 mg m(-2) and etoposide 100 mg m(-2), all administered intravenously (i.v.) on days 1-3 every 3 weeks) with G-CSF support. After three cycles, patients were submitted to radical surgery or received two additional courses of the ICE regimen and/or curative radiotherapy. Grade 3-4 neutropenia occurred in 21% of 114 evaluable courses, but was of short duration, leading to neutropenic fever in 5% of the courses. Severe thrombocytopenia and anaemia were observed in 13% and 3% of the courses respectively. Non-haematological toxicity was generally mild with only two episodes of reversible renal impairment. The overall response rate after three chemotherapy courses was 69% (28 partial responses, one complete response). Ten patients (8/10 patients in stage IIIA, 2/33 patients in stage IIIB) underwent radical surgery. Median TTP for patients not undergoing surgery (n = 33) was 8 months (range 3-34+); median DFS for patients rendered NED by surgery (n = 10) was 26 months (range 1-54+). Median OS for the entire group was 12.5 months (range 2-57+). The ICE regimen is active in locally advanced NSCLC with acceptable toxicity and warrants further exploration as induction chemotherapy in larger series.