Doxifluridine, a new fluoropyrimidine derivative, was tested in a cooperative phase II trial by the Swiss Group for Clinical Cancer Research in advanced measurable colorectal cancer. The drug was given in a five consecutive day schedule by a bolus intravenous injection at a dose of 4 g/m2 per day and repeated every three to four weeks. Of 42 eligible patients, 40 had no previous chemotherapy. Response was defined in 27 patients having received two or more courses of doxifluridine. Seven responses (26%) were observed. Responses were seen only in sigmoid and rectum primary tumors. Toxicity consisted mainly of leukopenia (53% of the evaluable patients), nausea and vomiting (38%). Other toxicities such as dermatitis, myocardial injury, and hair loss were also observed. Doxifluridine has therapeutic activity, albeit limited, in advanced rectosigmoid adenocarcinoma.