Antibodies directed to the HBs antigen indicate viral clearance and the development of life‐long immunity in patients that recovered from HBV infection. In HBs antigen vaccine recipients anti‐HBs antibodies provide protective immunity. However, little is known about the regulation of this HBs‐specific antibody response. The existence of anti‐HBs‐secreting B cells was demonstrated using the highly sensitive ELISPOT technique compared with conventional ELISA in serum and cell culture supernatants. In the peripheral blood of patients with acute self‐limited hepatitis B, HBs‐specific B cells were demonstrated with a high frequency despite undetectable anti‐HBs serum antibodies. HBV‐immunized patients that had recovered from infection and vaccine recipients had significantly lower frequencies, whereas chronic HBV carriers and negative controls showed no anti‐HBs‐secreting B cells. Coculture experiments of isolated B and T cells revealed that the anti‐HBs antibody response was restricted to the presence of T helper cells, but not to identical HLA class II molecules. Allogeneic T cells derived from vaccine recipients or chronic HBV carriers stimulated the HBs‐specific B cell response in HBs vaccine recipients. Otherwise, isolated T helper cells could never provide sufficient help to induce the HBs‐specific B cell response in chronic HBV carriers. Furthermore, peripheral blood mononuclear cells (PBMC) of six out of 10 vaccine recipients, one out of five HBV‐immunized patients, but of no chronic HBV carrier showed a proliferative response to different HBs antigen preparations. This study demonstrated a high frequency of circulating anti‐HBs‐producing B cells in the early phase of acute HBV infection, but a lower frequency of HBs‐specific B cells years after resolution of HBV infection. In chronic HBV carriers, however, deficient HBs‐specific T and B cell responses were observed.