Specimens from 57 patients with acute or chronic hepatitis non-A, non-B (HNANB), mostly mild to moderate, were studied by light and, in 22 instances, by electron microscopy. They were compared to specimens of hepatitis A and hepatitis B on file or obtained simultaneously with the HNANB cases. In the HNANB material, two types of light-microscopic lesions were noted in the lobular parenchyma singly or in combination. One was an eosinophilic alteration of the hepatocytic cytoplasm associated with many acidophilic bodies. Conspicuous alteration were often accompanied by microvesicular steatosis. This lesion was associated with nuclear particles detectable by electron microscopy. The second lesion consisted of sinusoidal cell activation which was prominent in some cases. From experiences with chimpanzees, these features were tentatively considered to be stages of the same process. Both lesions were associated with portal and usually mild periportal inflammation which was not related to the degree and type of parenchymal reaction. They were also observed in chronic stages, making the differentiation between acute and chronic HNANB difficult. Active hepatitis B seems to differ from HNANB primarily by the conspicuous presence of lymphocytes in the lobular parenchyma often in contact with hepatocytes, acidophilic bodies, and a more uniform portal inflammatory reaction. In hepatitis A, hepatocellular injury was conspicuously periportal. In HNANB, a cytopathic effect rather than lymphocytic immune attack appears to be of greater significance than in the other forms of viral hepatitis. The recurrence of lobular mainly eosinophilic changes may explain chronicity.