The purpose of this study was to review the efficacy of a protracted venous infusion of 5-fluorouracil (PVI 5-FU)-based chemotherapy in advanced small bowel adenocarcinoma. Data on all patients with small bowel malignancy who were seen at a single institution over a 5-year period were retrieved from the gastrointestinal unit and hospital databases, and these cases were reviewed. Eight patients with advanced small bowel adenocarcinoma received PVI 5FU-based chemotherapy. The overall response rate in assessable patients was 37.5% (3/8). The median overall survival was 13 months (range 1-28), and progression-free survival was 7.8 months (range 0-15). Overall, the treatment was well tolerated and symptomatic benefit was seen. In conclusion, PVI 5-FU has activity in this disease. This should be assessed either as a single agent or as part of a combination regimen such as epirubicin/cisplatin/PVI FU (ECF) in a multicentre randomized study.