In a prospective, randomized study a combination of 5-FU, Cyclophosphamide, and Methortrexate (FC-MTX) was compared to a similar combination (FC-CCNU) in which CCNU replaced Methotrexate. Of the 54 patients with metastatic colorectal carcinoma entered, 47 were evaluable. Toxicity was similar for the two regimens and was acceptable. No complete responses occurred. No difference in partial response (PR) 2/24 for FC-CCNU vs. 3/23 for FC-MTX, stable response 16/47 overall, or progressive disease 26/47 overall, was observed. Duration of PR was three to ten months. The overall median survival was six months, three months for non-responders and 11 months for responders. These drug combinations employing 5-FU do not improve upon the results reported with 5-FU alone in the treatment of metastatic colorectal carcinoma.