Interferons have been shown to increase in vitro cytotoxicity of platinum compounds. The Hoosier Oncology Group has conducted a Phase II clinical trial to determine if interferon alpha-2a (IFN-α-2a) given in combination with carboplatin (CBDCA) can increase response rates or survival in patients with metastatic or recurrent inoperable non-small-cell lung cancer. Forty-four patients with no prior chemotherapy and high KPS (80–100) were enrolled. CBDCA 400 mg/m2 was given intravenously on day 1 and IFN-α-2a 9 million units was given subcutaneously on days 1, 3, and 5. Treatment was administered every 4 weeks until onset of progressive disease or to a maximum of 4 courses: 37 patients (84%) received at least 2 courses, whereas only 16 (36%) received the full 4 courses. Dose-limiting toxicities were leukopenia (27%) and thrombocytopenia (20%) attributable to CBDCA. Grade 2–3 anemia occurred in 32%. Only 4–7% of patients experienced severe fever, fatigue, or flu-like symptoms attributable to interferon administration. Of 41 patients evaluable for response, there were no complete responses and only 3 (7.3%) partial remissions. The overall median survival was 6 months. The combination of CBDCA and IFN-α-2a given in this dose and schedule does not appear to have superior activity compared to CBDCA alone in patients with non-small-cell lung cancer.