Influenza subunit vaccines are poorly immunogenic in unprimed lower animals and man and methods were sought to potentiate the humoral response. Influenza B intact virus vaccines potentiated the antibody response of hamsters to purified vaccines containing influenza A hemagglutinin and neuraminidase subunits. The levels of anitbody induced were at least as high as those induced by equivalent doses of whole virus. Similarly, intact heterologous influenza A virus vaccine (A/Victoria/3/75 [H3N2]) potentiated the antibody response of hamsters to A/NJ/76 [Hswl NI] subunit vaccines but large doses of intact virus were required. Considerably lower doses of homologous intact A/NJ/76 [Hswl NI] potentiated the antibody response of hamsters and sero-negative people to subunit vaccines. This suggests that future influenza subunit vaccines for use in seronegative people should contain a minimal dose of whole virus vaccine sufficient to potentiate the immune response to the subunits but insufficient to be reactogenic. A synthetic water soluble adjuvant (N-acetyl-muramyl-L-alanyl-D-isoglutamine) was also shown to potentiate the immune response of hamsters to A/NJ/76 [Hswl NI] influenza virus subunit vaccines.