Forty-two patients with measurable advanced colorectal cancer were treated with sequential methotrexate (MTX) and 5-fluorouracil (5-FU), followed by folinic acid rescue. Twenty-one patients had received prior chemotherapy, mainly 5-FU (group 1) and remaining 21 patients had not been previously treated by cytotoxic agents (group 2). Two different treatment schedules were used. Regimen I (27 patients): MTX 250 mg/m2 was infused over 1 hour. Two hours from start 5-FU 600 mg/m2 was given as intravenous bolus. Folinic acid rescue started 24 hours after MTX infusion. Regimen II (15 patients): MTX 250 mg/m2 was given as 1-hour infusion. Three hours after the start of MTX a 46-hour 5-FU infusion (2000 mg/m2) was started. Folinic acid rescue as in regimen I. The chemotherapy courses were repeated every second week. After 3 cycles only one patient had partial response, 33 had no change and 8 progressive disease. The median time until progression was 2 1/2 months in group 1 and 4 months in group 2. The median survival was 7 months in group 1 and 10 1/2 months in group 2. Almost identical results were obtained by the two treatment schedules. The toxicity of both regimens was low.