Intra-arterial infusion of 5 FU is used in the treatment of a variety of neoplasms. Direct infusion of 5 FU into the arterial blood supply of the tumor allows the dose to be increased while avoiding the expected increase in systemic side effects. However, organs and tissues supplied by the vasculature infused, experience disproportionate toxicity. At our institution, between January, 1977, and October, 1980, 411 patients received intra-arterial infusions of 5 FU through percutaneously-placed catheters positioned within the hepatic artery. Sixty-three percent of these patients developed signs or symptoms thought clinically to represent gastrointestinal toxicity. In 25% of these, symptoms were sufficiently severe to warrant GI evaluation; 67% of the latter demonstrated morphologic changes of the stomach and small bowel attributable to 5 FU toxicity. In 20% of the 411 patients, it was necessary to stop the 5 FU infusion because of gastrointestinal toxicity. Abnormalities were predominantly confined to the stomach and duodenum and consisted of; 1) loss of distensibility; 2) hypersecretion; 3) mural and mucosal thickening; and 4) ulceration. These changes developed within two weeks after the start of 5 FU infusion and occurred in portions of the gastrointestinal system supplied by the vasculature being perfused. The rapid onset and distribution of the changes implicates 5 FU as the etiologic agent. In this report, we will describe and illustrate the changes seen in this group of patients. In our opinion, these abnormalities are best demonstrated through the use of double contrast examinations. In patients receiving intra-arterial infusion of 5 FU who develop gastrointestinal signs or symptoms, these studies should be promptly performed.