We performed a phase II study to assess the efficacy and toxicity of the cisplatin-UFT-leucovorin (LV) combination in patients with advanced non-small-cell lung cancer (NSCLC). Twenty-five patients with measurable disease who had not received prior chemotherapy were entered into the trial. The therapeutic regimen consisted of cisplatin 90 mg/m(2) and i.v. LV 500 mg/m(2) on day 1, followed by oral UFT 390 mg/m(2)/day (in two doses on days 1 through 14. Patients also received oral LV 15 mg/12 h on days 2 through 14. Seventeen patients required reduced doses of UFT (200 mg/m(2) due to toxicity. Courses were repeated every 28 days for a minimum of three per patient. Three of 25 patients (12%) achieved a partial response (95% CI: 2.6 to 32.2%), two with 390 mg/m(2)/day and one with 200 mg/m(2)/day of UFT. The main side effects were hematological and gastrointestinal. In the courses including 390 mg/m(2)/day of UFT, grade 3-4 toxicity was leucopenia in 18% of the courses, nausea/vomiting in 27%, and diarrhea and epigastralgia in 13% each. Grade 3-4 toxicities for 200 mg/m(2)/day of UFT were leucopenia 2%, nausea/vomiting 9% and diarrhea 7%. In conclusion, this regimen cannot be recommend for the treatment of advanced NSCLC due to its low response rate and high toxicity.