Two hundred thirty-seven patients with small cell lung cancer (SCLC), who had responded to induction chemotherapy and radiotherapy, were randomly assigned to receive low-dose natural interferon-alpha (nIFN alpha) for 6 months; or 6 cycles of maintenance chemotherapy (CAP); or no maintenance therapy (control group). Although there was no difference in median survival between the groups, there was a significant difference (p = 0.04) in the long-term survival of patients with limited disease, in favour of nIFN alpha maintenance therapy. This finding is now confirmed by a further analysis of the most recent data. Ten percent of patients in the IFN group survived for five years or more, but the 5-year-survival rate in the CAP and control groups was only two percent. All long-term survivors had good performance status. The majority had limited disease and had achieved a complete response to the induction therapy. These results suggest that interferon-alpha improves the long-term survival of SCLC patients for whom other prognostic factors are favorable.