The authors report on a case of cardiotoxicity observed during a protocol including a 5-day continuous infusion of 5-fluorouracil; anginal manifestations recurred during a second treatment course. Coronary angiography, thallium scintigraphy and methergine test were all normal. An attempt to prevent the recurrence of such manifestations using a calcium inhibitor and nitroderivatives was unsuccessful. In connection with this case, six other with anginal manifestation and four sudden deaths under the same protocol, a review of the relevant literature is included in the discussion on the factors that may favor cardiotoxicity and the different etiopathogenic hypothesis. The generally accepted hypothesis is a coronary spasm but a direct cardiotoxicity of 5-FU cannot be. The only therapeutic possibility appears to be the definitive halt of 5-FU after the onset of such manifestations.