Two regimens of 5FU and folinic acid in the treatment of metastatic colorectal cancer were retrospectively analyzed. 33 patients received the high dose (HD) schedule (5FU 370 mg/m2 and Folinic Acid 200 mg/m2 i.v. on D1-5, every 4 weeks), 61 patients received the low dose (LD) schedule (5FU 400 mg/m2 and Folinic Acid 20 mg/m2 i.v. on D1-5, every 4 weeks). One patient in each group achieved a complete response, the overall response rate was 28% and 11% for the HD and LD groups, respectively. The median response duration was 183 days for the HD and 112 days for the LD group. The median survival duration was 387 days for the HD and 405 days for the LD group. The response rate and duration of response were higher in the HD group though this did not reach statistical significance. There was no difference in overall survival between the two patient groups. Neutropenia and gastro-intestinal symptoms were the most common toxicities, they were equal in both groups. One patient (3%) in the HD and 5 patients (9%) in LD group discontinued treatment due to toxicity. There were no treatment related deaths. It is concluded that low dose folinic acid in combination with 5FU is effective and produces similar toxicities as high dose folinic acid. It is concluded that low dose folinic acid in combination with 5FU is an effective alternative to high dose regimen in the palliative management of patients with metastatic colorectal cancer. However though it did not reach statistical significance the high dose regimen was associated with a higher response rate. This could have a significant effect when the combination is used in the adjuvant treatment of high risk patients.