Dogs immunized parenterally with purified cholera toxin plus adjuvant had elevated titers of antitoxin in serum for 18 months and were protected against challenge with viable Vibrio cholerae for 10 months. Parenteral immunization with formalinized cholera toxoid or natural toxoid resulted in lower titers of antitoxin, and protection induced by the former lasted for five months. Dogs previously immunized parenterally with formalinized toxoid were given oral toxoid after protection due to parenteral immunization had disappeared. No rise in serum antitoxin occurred, but the animals were again highly protected against challenge with viable V. cholerae. After parenteral immunization, serum antitoxin correlated with protection only when the titer was high. The lack of correlation at lower titers of antitoxin in serum and the restoration of protection after oral “boosting” without a concomitant change in titer of antitoxin in serum suggest that protection by antitoxin is due, in part, to locally derived intestinal secretory antibody.