Purified human hepatitis B immunoglobulin (HBIG) was complexed to plasma derived hepatitis B vaccine (HBVac) at different concentrations and used to immunize Balb / c mice. An enhanced humoral immune response was observed when HBVac was complexed to HBIG in excess of antigen, compared to that immunized with the vaccine alone. Proliferation of splenic lymphocytes was detected when mice were immunized with HBIG complexed to HBVac (0.2-1 mug), whereas in mice immunized only with HBVac at one microgram, no lymphocyte proliferation was observed. The enhanced immunogenicity of HBIG: HBVac is T cell dependent. The importance of using critical ratio of HBIG and HBVac is indicated, and future application of this complex for vaccination of low- or nonresponders to the present HBVac, as well as for treatment of chronic hepatitis B patients is discussed.