Despite increasing evidence that coronary collaterals can prevent or limit the size of myocardial infarction it is not known how these collaterals develop. Whereas normal human pig and rat hearts have only a small number of coronary to coronary collaterals, 3 to 40 microns in size, normal dog heart collaterals are numerous and are 100-200 microns in size. In response to progressive narrowing of a coronary vessel over 5 days. canine vessels not only dilate but grow larger by a process involving cell division in all 3, layers of the vessel wall. It is not known whether ischemia triggers small vessel proliferation that is seen in embryogenesis and tumor angiogenesis. In humans with coronary artery disease, large interarterial collaterals are sometimes seen but it is not known whether these are due to expansion of pre-existing interarterial arterioles or whether they represent the final process of vascular remodeling following capillary proliferation. Therefore, as a preliminary step to studying the vasoproliferative response to ischemia without infarction, we studied the early proliferative response to acute myocardial infarction produced by coronary ligation in rats. In the nonoperated and sham operated controls we were are to confirm the very lows level of cell proliferation in the normal heart. However, an increase in labeling began by 48 hours in the border zone of the infarct, in fibroblasts and capillary and venular endothelial cells. By 48 hours there was intense labeling which extended into the non- inflamed nonischemic tissue, where it was seen only in the capillaries and venules. Thus, these data suggest that in myocardial infarction neovascularization begins very early and is found mostly in capillaries and venules as is the case in tumor angiogenesis. This suggests that the cellular physiology and biochemistry of angiogenesis are applicable to myocardial infarction. Furthermore, these growth responses occur sufficiently quickly to influence such events as infarct extension, expansion or rupture. Current studies are designed to see if this is true of myocardial ischemia as well.