Most individuals with viral hepatitis, type B, acquire a serum antigen (hepatitis-B antigen [HB Ag])1 at some time during the incubation period or the acute phase of the disease. Serial sera from 88 patients with viral hepatitis, type B, were examined for antibodies against HB Ag (anti-HB Ag) by passive hemagglutination (PHA) and radioimmunoassay (RIA) methods. Seventy individuals (79.5%) were found to develop serum anti-HB Ag at some time after exposure. Overt occurrences of hepatitis were usually followed by primary-type anti-HB Ag responses. However, early- or secondary-type anti-HB Ag responses were seen in 17 individuals who subsequently developed clinical hepatitis. Most individuals who were resistant to infection after parenteral exposure to materials known to transmit hepatitis had secondary antibody responses. We conclude that primary antibody responses to HB Ag are common after viral hepatitis, type B, and that protective immunity frequently but not invariably follows early exposure to hepatitis-B virus.