Hepatitis A virus (HAV) is transmitted by the fecal-oral route. The virus crosses through the gastrointestinal tract by an uncharacterized mechanism and travels to the liver, where it replicates in hepatocytes. It is released into the bloodstream and is simultaneously present in the bile and shed in the feces. Fecal shedding and viremia are maximal at the onset of liver function abnormalities and terminate about the time humoral immunity is detected, ∼28 days after exposure. IgM, IgA, and IgG anti-HAV antibodies are usually present at onset of symptoms. Although the IgM response becomes undetectable usually within 6 months, IgG responses frequently persist for life, providing protection against reinfection. Pre- and postexposure immunization with pooled human serum immunoglobulin (ISG) is ∼90% effective in preventing hepatitis A. Recipients of ISG have very low levels of detectable anti-HAY antibodies, and vaccines that elicit anti-HAY levels comparable with those produced by ISG should confer similar protection.