Rat corneas were cauterized chemically, and the induced neovascularization was studied by scanning electron microscopy of vascular casts. Casts were prepared by filling the pericorneal and intracorneal vessels with an acrylic monomer by an intracardiac injection. The initial response to injury was a vasodilation of pericorneal vessels and the appearance of impressions in the walls of veins and venules consistent with those of marginating leukocytes. The first new vascular buds emerged from the pericorneal venules and capillaries at 27 hours after injury. These sprouts lengthened and multiplied by 72 hours to produce a rich anastomosing plexus. New vessels were not seen arising from arteries and arterioles. By 7 days, numerous channels reached the cautery site and, by 13 days, many of the redundant intracorneal vessels had regressed leaving large looping channels connecting either with a pericorneal artery or a vein. The casts of those continuous with the artery had surface features suggesting arterial or arteriolar differentiation, whereas the smooth surfaces of the remaining channels were consistent with those of veins or capillaries. Transmission electron microscopy confirmed this differentiation by documenting intracorneal vessels with the smooth muscle and prominent endothelial cell nuclei which characterize arteries and arterioles. Vascular casts have several advantages in the study of neovascularization. They depict the three-dimensional characteristics of new vessel formation and reflect the vascular and cellular events in the accompanying acute inflammatory response; define more readily than histologic sections the time that the first new buds appear; emphasize capillaries and venules as the predominant source of new vessels; and suggest that certain new intracorneal vessels assume morphologic features of arteries or arterioles, whereas others retain capillary or venous characteristics.