Previous studies have shown that cholera, as well as protective immunity against infection with Vibrio cholerae, can be induced in the rabbit. This protection is long-lasting (up to 30 months) and is characterized on challenge by rapid, symptom-free disappearance of V. cholerae from the intestine; we therefore believe this to be vibriocidal protection. In this study, we analysed the humoral and secretory immune response against various subcellular V. cholerae components in vibriocidally protected, non-vibriocidally protected, and unprotected animals. Only vibriocidal protection was found to be associated with high levels of biliary IgA directed against lipopolysaccharide O antigen. We did not find such a correlation between either type ot protection and response in serum. Therefore, anti-lipopolysaccharide antibodies are essential in protection against experimental infection with V. cholerae.