Three days after herpes simplex virus inoculation, an increased amount of DNA and RNA was observed in the superficial epithelium cells of rabbit cornea. Histochemical staining demonstrated the development of acid mucopolysaccharides and the destruction of reticulin. In the early stages, on rare occasions, giant polykaryocytes with multiple micronuclei were seen. From 1 week after infection, more and more cells became rounded and shrunken. Cytoplasm of these cells might contain DNA diffusely interspersed with RNA. This DNA is probably viral in nature. The nuclei of these cells varied in shape, size, and staining intensity. Nuclear fragments were often observed in the cytoplasm. Stainings for acid mucopolysaccharides were strongly positive in the rounded cells. These cells fused to form syncytia Variable-sized pseudopodialike processes containing DNA and RNA extend from some of the rounded and liquefied cells toward other cells. In the later stages, development of ghost cells was seen. Histochemical methods demonstrated the deposition of acid mucopolysaccharides on their cell membranes. Necrosis was more often present in the late stages. Nuclear debris and deformed cells were encountered in such areas. On the healing of the keratitis, 3 months after inoculation, the cell cytology and staining reactions reverted to normal.