Some studies have shown that the combination of chemotherapy and interferon in non-small cell lung cancer (NSCLC) and other solid tumors is feasible and possesses antitumor activity. Our study was aimed at verifying whether the addition of recombinant human interferon alpha (rh-IFN alpha) to combined chemotherapy would be able to increase the response rate and survival of patients with NSCLC. Thirty-eight patients with previously untreated advanced NSCLC were evaluated in this study. Median age of patients was 57 years; performance status according to ECOG 0 and 1, 37 pts (97%); stage IIIB, 27 pts (71%); stage IV, 11 pts (29%). Histology was squamous cell carcinoma in 53%, adenocarcinoma 44% and large cell carcinoma 3%. Our schedule consisted of 80 mg/m(2) cisplatin IV, 100 mg/m(2) etoposide IV, 10 million U rh-IFN alpha IV and 10 million U rh-IFN alpha IV on first day of treatment, every 3 weeks. None of the patients had complete response. Partial response rate was 34%. Median response duration was 7 months (range 3-19 months), median survival time was 11 months (range 4-41 months). Twenty-nine percent of patients had grade 3 nausea and vomiting, 24% had grade 2 leucopenia, 5% had grade 2 cardiotoxicity, 2.6% had flu-like syndrome. According to these results, in advanced NSCLC, the addition of rh-IFN alpha did not increase the cisplatin-etoposide combined chemotherapy induced response rate and survival time.