The author presents seven patients with diabetes and cites from the literature seven patients with diabetes with probable enhanced 5-fluorouracil toxicity. In the author's seven patients, the amount of toxicity was directly related to the degree of hyperglycemia. In three of these patients who had the most severe hyperglycemia, toxicity was overwhelming, and led to death in two patients. In the 1960s, researchers showed, in a series of in vitro experiments, that glucose increased the cytotoxicity of 5-fluorouracil. The author concludes that patients whose diabetes is poorly controlled are at increased risk for severe 5-fluorouracil toxicity. New labeling instructions should advise caution in using 5-fluorouracil in patients with diabetes.