Autoantibodies directed against liver plasma membrane antigens have recently been described in patients with acute viral hepatitis, type A (AVH-A). To further investigate this phenomenon, the antibody against one such liver membrane antigen, liver specific membrane lipoprotein (LSP), was assayed in six marmosets orally inoculated with hepatitis A virus (HAV). Using a sensitive radioimmunoassay technique, anti-human LSP antibodies were detected in five of six animals. Two peaks of 125I-HLSP binding were observed: a minor peak at 20 days post-inoculation (dpi) in two animals, and a major peak at 38-45 dpi in five animals. There was no correlation between 125I-HLSP binding and liver histology score, ALT level, IgG concentration, anti-HAV P/N ratio, or E rosette lymphocyte count. A statistically significant correlation was observed, however, between 125I-HLSP binding and IgM anti-HAV antibody P/N ratios. 125I-HLSP binding was blocked by both marmoset and human LSP, but not by a marmoset kidney protein prepared in an identical manner. In summary, marmosets infected with HAV are a suitable animal model for the further investigation of anti-LSP autoantibody formation in AVH-A.