Eighteen patients with non-small cell lung cancer (NSCLC) who had previously received no systemic chemotherapy, were treated on this phase II study with interferon-alfa-2b 8 MU tiw, leucovorin 500 mg/m2 IVPB over 2 hours and 5-Fluorouracil 500 mg/m2 i.v. for 6 weeks followed by a 2-week rest. There were was no rest period for interferon. Median age of patients on this study was 63 years. Fatigue, nausea, and diarrhea were the most common toxicities. There were no grade IV toxicities and no treatment-related deaths. Seven partial responses (39%) with median duration of 4.5 months were seen. An additional patient has had stable disease/minor response for 12+ months. Median survival is 10 months. ALF has activity in NSCLC.