New active agents are needed to develop effective systemic therapy against Stage IIIB-IV non-small cell lung cancer (NSCLC). The aim of the present study was to assess the efficacy and toxicity of gemcitabine, a novel nucleoside analogue with significant preclinical activity, as a single-agent therapy. Forty-three patients with previously untreated Stage IIIB-IV NSCLC were included. Gemcitabine was administered intravenously over 30 min on Days 1, 8 and 15 of each 28-day cycle at a dose of 1250 mg m-2. Thirty-seven patients were evaluable for response. There were seven partial responses giving an overall response rate of 19% (95% confidence interval 8-35%). Median duration of response was 6 months. One-year survival and median survival for all patients were 33% and 8 months, respectively. Toxicity of the treatment was mild. World Health Organization (WHO) Grade 3-4 leukopenia was detected in 11% of the patients. Mild (WHO Grade 1-2) nausea was the most frequent subjective side-effect with a rate of 82%. Mild rash and peripheral oedema were typical side-effects of gemcitabine with rates of 19 and 9%, respectively. In conclusion, single-agent gemcitabine is an active and well-tolerated treatment for Stage IIIB-IV NSCLC patients.