We undertook a randomized trial in patients with advanced colorectal cancer, comparing 5-fluorouracil and leucovorin versus combination of these agents with additional cisplatin. Between July 1991 and October 1994, 21 patients with advanced measurable colorectal cancer previously unexposed to chemotherapy were randomly assigned to treatment with either 5-FU (500-750 mg/body) and LV (30 mg/body) for 5 days, or the combination of 5-FU and LV in the same daily dose plus cisplatin (10 mg/body). The overall responses were 30% and 36.3% for the 5-FU/LV and the 5-FU/LV/CDDP treatment arms, respectively. The three-drug combination appeared superior to 5-FU/LV for response duration. A comparative analysis of the toxicities experienced by the patients in the two treatment groups showed a comparable rate, although moderate leukocytopenia was prolonged in one patient treated with 5-FU/LV for 5 days. We conclude that the 5-FU/LV/CDDP treatment arm is an effective therapy for advanced colorectal cancer, but further attempts should be made to increase response rate, prolong response duration and assure effective therapy.