Natural immunity to hepatitis A virus (HAV) is complex and likely to involve several distinct arms of the immune system. There is evidence that natural killer cells, human leukocyte antigen (HLA)-restricted cytotoxic T cells, and antibody-secreting cells of B-cell lineage all play roles in the immune response to infection with HAV. However, antibody alone is sufficient to provide a high level of protection against clinical disease. A comparison of the serum levels of antibody to HAV (anti-HAV) following administration of immune serum globulin and hepatitis A vaccine may provide a useful estimate of vaccine efficacy. Such comparisons may be accomplished using solid-phase immunoassays for detection of anti-HAV. However, tests which measure antibody capable of neutralizing virus in vitro are generally more sensitive than solid-phase immunoassays. The use of endogenously labelled virus in radioimmunoprecipitation assays shows promise of providing an equally sensitive means of measuring antibodies which are reactive with HAV particles.