Antibody to hepatitis B core antigen (anti-HBc), which has been assumed to be a more sensitive indicator of hepatitis B virus replication than hepatitis B surface antigen (HBsAg), was detected in the sera of 26 of our 65 patients with HBsAg-negative chronic active hepatitis. Thus despite the absence of HBsAg the liver disease could be the consequence of chronic infection with hepatitis B virus in these patients. They differed, however, from a group of 35 patients with HBsAg-positive hepatitis in being older on average and having less active liver lesions. The two groups could represent either two stages of chronic infection with hepatitis B virus or two types of response to it.