Preliminary studies have shown bioactivity of interferons (IFNs) in the treatment of small-cell lung cancer (SCLC). The aim of the present study was to determine whether, in patients with advanced SCLC, a combination of recombinant IFN-alpha-2c and standard induction chemotherapy would improve response rates and survival at acceptable toxicity. Of the 85 patients recruited by 11 centres in Austria, 77 were evaluable for response after induction therapy; of these, 43 were randomized to receive the combined treatment (three cycles each of cyclophosphamide/vincristine/doxorubicin and cisplatin/etoposide plus subcutaneous IFN-alpha-2c), and 34 received chemotherapy alone. After the induction phase, patients in the IFN arm had higher rates of complete (30 vs 15%) and partial remission (42 vs 29%) than those who received chemotherapy alone. Accordingly, there was a lower rate of progressive disease in the interferon arm (21 vs 44%; p < 0.05). Whilst there were no significant differences in time to progression (7.6 vs 5.4 months) patients in the IFN arm survived longer than those in the chemotherapy arm (p < 0.02). Six of the patients treated with IFN (14%) survived for more than 2 yrs, whereas none in the chemotherapy arm did. We conclude that the addition of interferon-alpha-2c to induction chemotherapy may improve response rates and survival in advanced small-cell lung cancer.