Clinical trials have been initiated examining the combination of fluorouracil (5-FU) and recombinant interferon alfa-2a (rIFN-2a) in the treatment of advanced colorectal carcinomas. An early trial reported a response rate of 76%, encouraging further investigation. Clinical trials have used 5-FU administered as a continuous intravenous infusion, 750 mg/m2 per day for 5 consecutive days, followed by weekly bolus administration of 5-FU 750 mg/m2. Recombinant interferon alfa-2a, 9 million units, was administered subcutaneously three times weekly. Of 45 evaluable patients treated at The University of Texas M. D. Anderson Cancer Center, a response rate of 35% (95% confidence interval, 22%, 50%) was observed. Twenty-five percent of patients developed grade 4 toxicity and 82% developed grade 3 toxicity. The median survival was 16 months. Investigation of this combination will require randomized trials to further assess activity in relation to alternative treatments.