Resistance to growth of Vibrio cholerae at the mucosa of blind intestinal loops developed in rats after intestinal or parenteral exposure to live organisms or other antigenic materials. Simultaneous serological studies suggested that neither serum vibriocidal activity nor intestinal mucus antibodies are likely to provide a direct test of antibacterial immune status. Challenge of rats 4 weeks after one dose of antigen may reveal a form of immunity that is not related to antibodies in the intestine and possibly is analogous to long-term immunity expressed in man following infection with the organism. This immunity has not been attributed to lipopolysaccharide (LPS) antigen and does not appear to involve flagella-associated antigens; involvement of antigens other than LPS, such as protein antigens of the outer membranes of V. cholerae, has not yet been substantiated. Separation of monomeric sub-units of outer-membrane proteins by hydrophobic interaction high pressure liquid chromatography has revealed significant quantitative differences among preparations derived from the common serotypes of the organism. These differences may be sufficient to explain the better protection observed when homologous serotypes were used for immunisation and challenge in the long-term resistance model.