A total of 92 patients with small-cell lung cancer (SCLC) were randomized to receive cisplatin (80 mg/m2, day l)/etoposide (100 mg/m2, days 1, 3, 5) (PE) or cisplatin (80 mg/m2, day l)/etoposide (100 mg/m2, days 1,3, 5)/ifosfamide (2 g/m2, days 1,2, 3) (PEI) combination chemotherapy. After 2 courses of chemotherapy, patients with limited disease (LD) received chest irradiation of 40-50 Gy. Of the 89 patients who could be wholly evaluated, the overall response rate was 78% for PE and 74% for PEI therapy (NS). For all patients the complete response (CR) rates were 14 versus 21 %, respectively, and 22 versus 30% for LD. However, the median survival times for all patients were 55 weeks for PE therapy versus 56 weeks for PEI therapy (NS). The 2-year survival rates were 15 and 17%, respectively, for all patients (NS). There was no difference in the duration of response between PE and PEI therapy in cases with CR or partial response. However, severe leukopenia ( < 2,000/mm3) occurred more often after PEI (73%) than after PE (44%) therapy (p < 0.05). These results suggest that PEI is not superior to PE chemotherapy in SCLC. The use of ifosfamide in multimodality treatment regimens needs to be studied further.