Twenty-one patients with limited (12 cases) or extensive (9 cases) small cell lung cancer entered a pilot study with adriamycin (ADM) plus ifosfamide (IFX) as first line treatment for six planned cycles. ADM was administered at the dose of 60 mg/m2 iv push on day 1 and IFX at 3 g/m2/iv in 1-hour infusion on days 1 and 2. To prevent IFX-induced hemorrhagic cystitis, mercaptoethane sulfonate sodium (Mesna) was given after the administration of IFX at the dose of 500 mg/m2 by iv push four times (hour 0, 4, 8, 12) on days 1 and 2. In the absence of disease progression, chemotherapy was repeated every 3 weeks for 6 cycles. All patients were evaluable for analysis of response, toxicity and survival. The overall response rate clinically and radiologically assessed after four treatment cycles was 95.3% (CR 28.6%, PR 66.7%). However, by continuing the same drug treatment up to the sixth cycle, 7 of 14 partial responders showed tumor progression within the intrathoracic region. Therefore, at the end of the planned chemotherapy program the partial remission rate fell to 33.3%, for a total remission rate of 61.9% and a median total survival of 9 months (range 5 to 36+). The regimen was well tolerated with only one case presenting hemorrhagic cystitis. The results achieved with this drug combination appear comparable to those obtained with other conventional regimens. However, the high response rate achieved after four cycles and the low incidence of marrow toxicity suggest the use of this regimen for a short period with increased dose levels.