This chapter considers the natural history of infection and what is known about the pathology and pathogenesis of hepatitis A in experimentally infected animals. Clinical illness has proven to be an unreliable indication of infection in nonhuman primates. Infected animals occasionally become listless, lose their appetite, and develop ruffled hair. By contrast, with outbreaks of hepatitis A in animal colonies, diarrhea is rarely a feature in experimentally transmitted infections, suggesting that this symptom is caused by concurrent infection with other enteric pathogens. Many of the studies of hepatitis A infection in nonhuman primates have been undertaken with five well-documented strains of HAV; Mir Serum pool 1 (MS-1), SD11, CR326, HM175, and PA33; which were derived from naturally acquired infections in man and Aotus monkeys. The MS-1 and MS-2 serum pools were derived from a child at Willowbrook State School who developed two separate attacks of viral hepatitis.