Secretory IgA antibodies in mucosa are known to play an essential role in protection against various infectious agents. To enhance the induction of protective mucosal antibodies, influenza HA vaccine was inoculated intranasally into mice with the B subunit of cholera toxin (CTB), which is known to be an excellent mucosal self-adjuvanting molecule. This combination resulted in high levels of antiviral IgA antibodies in nasal secretions and enhanced serum haemagglutinin-inhibiting (HI) antibodies 4 weeks after inoculation, compared with the inoculation of vaccine alone which induced only a low level of HI serum antibodies and no local IgA antibodies. (Subcutaneous or intraperitoneal inoculation of the vaccine with CTB failed to induce detectable nasal antiviral IgA antibodies). Levels of nasal IgA and serum HI antibodies increased in a dose-dependent fashion with increasing nasal doses of both vaccine and CTB, and correlated with the degree of protection against viral challenge. A greater protective effect was seen with cholera toxin than with its B subunit. Moreover, a second administration of vaccine alone, 4 weeks after the inoculation of the vaccine with CTB, elevated the level of the antiviral IgA nasal antibodies to 10-100 times higher than that of the primary response. These results suggest that either CT or CTB could be used as a potent adjuvant to induce protective secretory antibodies by nasal vaccination against pathogens impinging on respiratory mucosa.