The feasibility of combining UFT plus leucovorin (LV) with alternating irinotecan and oxaliplatin was investigated in the first-line treatment of patients with advanced colorectal cancer. Twenty-five patients, median age 63 (range 24-79) years, World Health Organisation performance status 0-2 and median four marker lesions, received irinotecan 180 mg m(-2) on day 1, oxaliplatin 85-100 mg m(-2) on day 15 and UFT 200-300 mg m(-2) day(-1) with LV 90 mg day(-1), days 1-21 of a 28-day cycle. Patients were treated in cohorts of three. At the highest dose (irinotecan 180 mg m(-2), oxaliplatin 100 mg m(-2) and UFT 300 mg m(-2) day(-1)), three of four patients experienced grade 3 toxicity. Diarrhoea, lethargy and vomiting were dose-limiting. Three of nine patients had grade 2 toxicities at the maximum tolerated dose (irinotecan 180 mg m(-2), oxaliplatin 100 mg m(-2) and UFT 250 mg m(-2) day(-1)). There were no grade 3 toxicities in the first month of therapy. The overall response rate was 71% in 21 evaluable patients; progression-free survival was 8.8 months. Alternating irinotecan and oxaliplatin plus UFT is an effective and well-tolerated first-line treatment for patients with advanced colorectal cancer. We recommend a dose of irinotecan 180 mg m(-2) on day 1, oxaliplatin 100 mg m(-2) on day 15 and UFT 250 mg m(-2) day(-1) with LV 90 mg day(-1) on days 1-21 of a 28-day cycle for future studies.