BACKGROUND Non-small cell lung cancer (NSCLC) has a relatively low response rate to systemic chemotherapy. Recently, several investigations have shown that interferon may augment the cytotoxic effect of chemotherapeutic agents and may improve the result of chemotherapy in treating cancers. METHODS An open-label noncomparative phase II study investigated the efficacy and safety of combined chemoimmunotherapy for NSCLC using IFN-alpha, given by intramuscular injection with 9 million units thrice a week for a maximum of 26 weeks, and cisplatin by intravenous infusion, 100 mg/m2, every 4 weeks for a maximum of 6 cycles. Ten patients, with histology-confirmed NSCLC at stage IV of their diseases were enrolled. They included 5 men and 5 women, with an average age of 53.7 year. Five of them had adenocarcinoma; the other five had squamous cell carcinoma. RESULTS Five patients, including two patients with squamous cell carcinoma and three with adenocarcinoma, obtained a partial response (response rate 50%). The time needed to achieve a sustained response ranged from 5 to 13 weeks with a median of 8 weeks. The response duration ranged from 14 to 37 weeks with a median of 20 weeks. The overall survival time for the ten patients ranged from 2 to 20 months with a median of 8 months. All 10 patients needed dose modifications of IFN-alpha and/or cisplatin because of myelosuppression and/or impaired renal function. Other frequently encountered side effects included gastrointestinal disturbances and a flu-like syndrome, but these were well tolerated. CONCLUSIONS These preliminary results indicate that chemoimmunotherapy with IFN-alpha and cisplatin can be an effective alternative therapy for patients with advanced NSCLC, but there are significant side effects.