A new type of hepatitis B virus (HBV) infection has been encountered in Senegalese infants and French adults characterized by serum hepatitis B surface antigen (HBsAg) without antibodies to the core antigen (anti-HBc). As the infection is not associated with the presence of the e antigen, it differs from HBV in its core antigen. After the loss of HBsAg, neither anti-HBc nor antibodies to HBsAg (anti-HBs) become detectable. This new infection (called HBV2 as opposed to the classical HBV1 infection) was found in infants with anti-HBs, either naturally acquired or produced by immunization against HBV. The use of monoclonal anti-HBs antibodies showed that two epitopes of HBV1 surface antigen could be detected in HBV2-positive sera. HBV DNA sequences could only be found in one of 15 HBV2-infected children using a DNA-DNA hybridization procedure; low levels of HBV DNA were also detected in 58% of the HBsAg-positive adult sera tested. If this new infection, apparently related to HBV1, is shown to cause chronic liver disease, hepatitis B vaccine should also contain surface antigen from HBV2.