An enhanced antineoplastic effect of 5-fluorouracil in patients with advanced colorectal cancer has been produced either by combination with folinic acid or administration by continuous infusion. Thirty-seven patients with advanced measurable colorectal cancer received high-dose folinic acid (LV 200 mg/m2) followed by 5-fluorouracil i.v. bolus (300 mg/m2) and continuous infusion (300 mg/m2) on days 1 and 2 then 14 and 15 every 4 weeks. In the absence of toxicity, 5-FU was increased to 400 mg/m2 i.v. bolus and continuous infusion at course 2 and to 500 mg/m2 at course 3 and from course 4 maintained at 500 mg/m2. Responses were: complete responses: 1 (2.7%), partial responses: 19 (51.4%), no change: 8 (21.6%) and progressive disease: 9 (24.3%). CEA decrease was correlated with response. Median duration of response was 11 months. Median survival was 18 months, 21% of the patients were alive at 2 years. Toxicity was low, with diarrhea in 17% and nausea in 11.5% of the patients. LV-5-FU bolus and continuous infusion is safe and has definite activity in metastatic colorectal cancer.