The feasibility of measuring the extent of hypoperfused myocardium and the infarct size was examined in rat hearts after occlusion of the left coronary artery. The extent of hypoperfused myocardium was examined by autoradiography and after perfusion with fluorescent microspheres. Both methods appeared unreliable in this model. Triphenyltetrazolium chloride (TTC) staining, however, provided a distinct demarcation line between viable myocardium, which was stained red, and the necrotic myocardium, consistent with the ultrastructural border between normal and severely damaged myocytes 5 h after coronary occlusion. TTC staining gives the best demarcation of ischemic tissues. In verapamil-treated rats, there was an apparent reduction in infarct size as compared with untreated rats; 20% reduction in infarct size 5 h after coronary occlusion and 12% reduction after 24 h. There was, however, a large postoperative mortality among the verapamil-treated rats. These problems, and the nonuniform infarct size in rats, may in part explain why infarct size limitation by verapamil has been reported from rat experiments, but not from clinical trials.