Cholera toxin from Vibrio cholerae has been shown to increase the secretory immune response when given orally with some antigens in mice and rabbits. The present study was designed to determine if cholera toxin was also an effective mucosal adjuvant in chickens. Tetanus toxoid was chosen as a model antigen, and response was measured by enzyme-linked immunosorbent assays of intestinal excreta, bile samples, and serum samples. Chickens given 20 micrograms of tetanus toxoid had a significant suppression of response when 20 or 50 micrograms of cholera toxin was given. Chickens given 100 micrograms of tetanus toxoid appeared to be mucosally tolerant, but there was apparent abrogation of the mucosal tolerance when 20 or 50 micrograms of cholera toxin was given. Cholera toxin apparently failed as a mucosal adjuvant in chickens but may have some anti-mucosal tolerogenic effect.