Two distinct antigen-antibody systems are associated with the hepatitis B virus: the hepatitis B surface antigen (HBsAg, Australia antigen) and antibody (anti-HBs) and the recently characterized hepatitis B core antigen (HBcAg) and antibody (anti-HBc, anti-core). HBsAg is found in the serum of patients acutely or chronically infected with the hepatitis B virus (HBV) and is represented on electron microscopy of such serum as 20 nm spherical and tubular structures and as the surface component of the 42 nm Dane particle. The core antigen of the HBV is associated with a 27 nm viral nucleocapsid particle present in the nuclei of infected hepatocytes and with the inner, core component of the Dane particle. These two HBV antigens have been shown to be antigenically distinct by immune electron microscopy. Immunization studies have demonstrated that both antigens are capable of eliciting distinct, humoral and cell-mediated immune responses in guinea pigs. Analysis of immune responses to HBcAg during the course of type B hepatitis provides a clearer understanding of this disease and anti-HBc may serve as a sensitive marker for the presence of the chronic HBsAg carrier state.