The distribution and the size of lesions evoked in rat heart by the injection of isoprenaline 30 mg/kg have been estimated in rat pretreated or not by various dosages of N-methyl-N-(beta-hydroxyethyl)guanidine O-phosphate (creatinol O-phosphate). It has been observed that the number of lesions was inequally distributed in the various parts of the heart. Creatinol O-phosphate pretreatment reduced both the number and the size of the reactive areas. The reduction of the number of foci was dose-dependent. The action of the lowest creatinol O-phosphate doses was increased by a pretreatment during 4 days instead of the 4 h pretreatment initially used. The size of the reactive area was also reduced but in a manner indicating an action of large creatinol O-phosphate dosages on the microcirculation. It is concluded that, due to its protective action against cardionecrosis, creatinol O-phosphate has great potential value in patients with myocardial infarction in whom the extent of the infarct size may be limited by an action on the jeopardized area.