To assess the epidemiologic characteristics of the population susceptible to hepatitis A virus (HAV) infection and determine the natural history of infection, a retrospective survey was done using banked serum specimens. A random sample of 4030 Alaska Natives statewide was selected, stratified by year of birth and community of residence. Overall, 1988 serum samples (49.3%) tested positive for antibody to HAV (anti-HAV). Past HAV infection was strongly age-related, increasing from 7% in persons born since 1975 to 85% among persons born before 1945. Prevalence of infection also varied between regions. In small communities, a clear demarcation typically existed between previously infected older persons and younger anti-HAV-negative persons. This indicated that village-wide outbreaks of HAV infection have been the norm and appear to be dependent on the presence of a young susceptible population. Widespread vaccination with hepatitis A vaccine to maintain a high proportion of young anti-HAV-positive persons may be successful in preventing future epidemics.