The activity and tolerability of gemcitabine and the non-overlapping toxicity of gemcitabine plus vincristine were the basis for testing this regimen patients with non-small cell lung cancer (NSCLC). Forty patients (25 male/15 female, median age 52 years) with stage IV NSCLC and a Karnofsky Performance Status score > or = 60 entered the trial. Patients received gemcitabine 1000 mg/m2 on days 1, 8 and 15 and vincristine 1.4 mg/m2 on days 1 and 15, every 4 weeks. The overall response rate was 16/40 (40%) (N = 40); with 2 complete and 14 partial responses; additional 14 patients had minor responses or stable disease. Median duration of remission was 4.5 months, and the median survival was 9 months. In two patients with grade 2 generalized vesicular rash and severe malaise, respectively, treatment-related toxicity led to early termination of treatment. Among patients treated for more than two months, vincristine doses were reduced/omitted for 55% of cycles because of grade 1-2 peripheral neuropathy. Myelotoxicity was frequent but rarely clinically significant. Mean platelet counts on day 1 of cycles 2,3 and 4 were significantly higher than the pre-treatment or post-treatment values. We conclude that vincristine plus gemcitabine is an an active and well tolerated regimen. Its interesting "platelet-saving" effect deserves further investigation.