A number of factors make it difficult to describe the evolution of morphological changes in the liver in a disease that varies in its severity from an asymptomatic or anicteric infection to massive necrosis of the liver. Thus, biopsy of the liver is not required during the incubation period of the infection in anicteric patients or in patients with the typical mild illness. Two features are constant in acute human viral hepatitis: (1) parenchymal cell necrosis and (2) histiocytic periportal inflammation. In general, the reticulin framework of the liver is well preserved except in some cases of massive and submassive necrosis. The liver cells show various forms of necrotic changes, which are usually multifocal, but necrosis frequently tends to be zonal with the most severe changes in the centrilobular areas. Individual hepatocytes are commonly swollen and may show ballooning, but they may shrink. A mononuclear cellular infiltration, which is particularly marked in the portal zones, is the characteristic mesenchymal reaction. This is accompanied by some bile ductular proliferation. In humans, it is not possible to distinguish between the changes in the liver in hepatitis A and B on morphological grounds.