The present phase I study was designed to determine the maximum tolerated dose (MTD) of epirubicin, administered every 3 weeks to patients with advanced non-small cell lung cancer (NSCLC), and combined with a conventional dose of vinorelbine [25 mg/m2 intravenously (i.v.) days 1 and 8] with or without the support of granulocyte-colony stimulating factor (G-CSF). 18 patients entered the study. The patients received the following four dose levels of epirubicin (i.v., day 1): 50 mg/m2 (3 patients) and 60 mg/m2 (6 patients) without G-CSF, 75 mg/m2 (3 patients) and 90 mg/m2 (6 patients) with G-CSF (5 micrograms/kg days 4-6 and 9-15). In the patients treated without G-CSF the MTD of epirubicin was 60 mg/m2 and leukopenia was the dose-limiting toxicity. In the patients treated with G-CSF the MTD was 90 mg/m2, myelotoxicity being the dose-limiting toxicity. We observed 1/3 partial response (PR) with epirubicin at the dose of 75 mg/m2 and 2/6 PR at 90 mg/m2. These results would indicate the usefulness of a phase II study with epirubicin at the dose of 90 mg/m2 in association with conventional dose of vinorelbine with the support of G-CSF in advanced NSCLC.