Scrapie is considered a prototype of the spongiform encephalopathies. This group of diseases is characterized by a prolonged incubation period, without symptoms, followed by an insidious onset of clinical disease leading to death. Attention was mainly focused on CNS pathology and reports of pathology in the retina were limited. Hamsters were inoculated intracerebrally with the scrapie agent and serially sacrificed to determine agent titers and pathologic changes in the eyes over time. Scrapie infectivity rises progressively in the eye to maximal levels between 6-8 wk after inoculation and then reaches a plateau. Ocular abnormalities are 1st visible 8 wk after infection. The process begins with a gradual loss of rod outer segments, after which progressive loss of rod inner segments and photoreceptor nuclei occurs. By 10 wk, only a vestige of the outer nuclear layer remains. Ultrastructurally, this destruction is attended by the presence of macrophages, although the importance of this finding is unknown. Later, Mueller cells increase their pericellular investment of remaining photoreceptor cell nuclei. The limitation of the lesion to the outer retinal layers suggests this tissue site may be important in the investigation of basic pathogenetic mechanisms in the spongiform encephalopathies.