Three patients developed anterior substernal chest pain in association with ischemic electrocardiographic changes temporally related to continuous infusions of 5-fluorouracil (5-FU). Two patients developed myocardial infarctions and one died. Cardiac toxicity of 5-FU may be more likely when the drug is given by continuous infusion in the presence of preexisting cardiac disease. The pattern of cardiac toxicity suggests cardiac ischemia most likely secondary to coronary artery vasospasm. Patients should not receive 5-FU by infusion if they have significant underlying coronary artery disease or if they develop anterior substernal chest pain while receiving the drug.