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Abstract: The importance of antibodies to cholera toxin (CT) versus desensitization of intestinal adenylate cyclase for protection against experimental cholera in the rat was investigated. Animals were immunized five times with CT either perorally or intravenously; antitoxic antibodies were measured in both serum and bile, and intestinal anti-CT-containing plasma cells (ACC) as well as eosinophilic leucocytes were counted. Both peroral and intravenous immunizations induced high levels of serum antibodies, while antibodies in bile appeared only after peroral immunization. The number of eosinophilic leucocytes in the intestinal mucosa increased in response to peroral immunization. CT-induced stimulation of intestinal adenylate cyclase was significantly suppressed, i.e., desensitized, after peroral immunization, but was equally stimulated in intravenous immunized and in control animals. A constant and long-lasting protection against CT-induced secretion was obtained after peroral immunization. This protection correlated neither to the concentrations of antitoxic antibodies in serum, nor to those in bile, nor to the number of ACC, but did correlate to the desensitization of adenylate cyclase.