Methotrexate (MTX) (250 mg/m2) was given as an i.v. infusion over 2 hr. At hour three and 23, 5-FU (500 mg/m2, maximally 1000 mg) was given as a bolus i.v. injection. The Leucovorin rescue was initiated hour 24. The chemotherapy course was repeated every 14 days for eight courses, then every third to fourth week. At least four courses of the regime were given to 50 patients with measurable advanced colorectal carcinoma. Toxicity was usually very mild but in seven patients an increase of serum creatinine was registered. Two of these patients had a severe period of uremia. With a more careful observation of kidney function, these episodes should have been foreseen. An objective response rate of 50% with six complete remissions (CR) and 19 partial remissions (PR) was found. Eighty-eight per cent (21/24) of the patients with tumour-related symptoms experienced symptomatic relief. The median response duration amounts to 5 months. It is concluded that the MFL regime is effective in inducing anti-tumour response in patients with advanced colorectal cancer.