Protection by prolonged administration of allopurinol against high-dose 5-fluorouracil (5-FU) administered with folinic acid in 74 patients with colorectal cancer was investigated. The dose of 5-FU was 700 mg/m2 per day for 5 days. Of 41 patients without previous chemotherapy, 1 had a complete response and 4 had partial responses (total 12%), 15 remained stable and 21 progressed. Mean duration of response was 7.4 (1.8-12.6) months. The most frequent toxicities were decreased granulocytes (13%), diarrhoea (37%), and stomatitis (35%), which were similar to the frequencies of other studies with lower doses of 5-FU without allopurinol. Prolonged administration of allopurinol thus gives some protection to patients with colorectal cancer who receive folinic acid plus high-dose 5-FU but responses were not better than those with conventional doses.