Using ultrahistochemical and immunohistochemical techniques, localization of acid phosphatase and cathepsin D was demonstrated in the retina and pigment epithelium of 1 to 42 day old RCS rats and its nonaffected congenic rat strain. Both enzymes are present in the pigment epithelium of the normal and dystrophic rat eye. As early as the age of 1 week, it was found that the lysosomes in the dystrophic rat retina are less stable in releasing acid phosphatase than those of control animals. Infiltration of cathepsin D into the subretinal space could first be detected with certainty in 2-week-old animals. The fragility of the lysosomal membrane and, therefore, the release of both enzymes became more pronounced as the animals aged. The findings of this study indicate that the instability of the lysosomal membrane in the RCS rat pigment epithelium may initiate degeneration of photoreceptors and pigment epithelium. The demonstration of cathepsin D activity has proved very helpful in revealing the physiological or pathophysiological condition of retinal pigment epithelium.