Cholera toxin was investigated as an adjuvant for anti-virus antibody responses in the respiratory mucosa of mice. Two methods of applying cholera toxin were evaluated: oral administration and intranasal administration. Oral immunization with Sendai virus in the presence of cholera toxin effectively primed for respiratory anti-viral antibody responses, whereas oral immunization with Sendai virus alone was ineffective in this respect. In nasal washes, IgA was the predominant anti-viral antibody enhanced by oral cholera toxin; in bronchoalveolar washes, the enhanced anti-viral antibodies included IgG, IgA, and IgM. Effects of direct administration of cholera toxin to the respiratory mucosa on respiratory anti-viral antibody responses depended on the method of anesthesia used during immunization. With inhalation anesthesia (ether), cholera toxin had no adjuvant effect on respiratory antibody responses to coadministered Sendai virus. In contrast, under parenteral anesthesia (i.e., intraperitoneal ketamine), mice which received cholera toxin and Sendai virus via the respiratory tract showed significantly higher anti-viral IgA and IgG antibody titers in nasal washes and IgG antibody in bronchoalveolar washes than mice which received the virus only.