Leprosy is the third leading cause of blindness worldwide; however, little is known about the ocular changes that occur during the disease process. We have studied the eyes of two nine-banded armadillos with experimental Mycobacterium leprae infection by light and electron microscopy. Both animals had been inoculated intracutaneously, one 5 years and the other 2 years previously. Light microscopy revealed invasion by acid-fast bacilli which were seen in keratocytes and mononuclear phagocytes in all layers of the corneal stroma. In both animals, large macrophage granulomas were observed in the deep stroma, which was vascularized. Acid-fast bacilli were also were found in macrophages and vascular endothelial cells. By electron microscopy, numerous bacilli were found in the keratocytes, macrophages, and Schwann cells of myelinated and unmyelinated axons, and in the endothelial cells of blood vessels. The localization of M. leprae and the presence of inflammatory cells in the ocular tissue of both animals suggest that the bacilli reach the eye by the neural and/or vascular route. One animal showed much more extensive disease and bacillary yield than the other, indicating that ocular involvement may be independent of the generalized infection. Further studies of early ocular involvement in the armadillo and other animals could help to clarify the pathogenesis of this potentially blinding infection.