A study was undertaken to elucidate the etiology of HBsAg-negative chronic hepatitis. From 37 individuals with HBsAg-negative chronic hepatitis, 11 had liver membrane auto-antibody (LMA) and were thus classified as autoimmune. 6 patients had anti-HBc, 1 of which was also positive for LMA. The majority of individuals with HBsAg-negative chronic hepatitis had antibodies to hepatitis A antigen (anti-HAV), in general at low titer. We conclude from our data that hepatitis A and hepatitis B virus infections are unlikely to play a significant role in inducing or maintaining HBsAg-negative chronic hepatitis. The etiological role of non-A non-B hepatitis agent(s) is difficult to estimate and must await the detection of appropriate markers for type non-A non-B hepatitis.