A chinchilla model has been developed in which experimental cholera can be predictably evoked without ligation of the gut. Chinchillas inoculated intraintestinally with 106Vibrio cholerae 569B organisms developed a broad spectrum of symptoms ranging from asymptomatic infection to severe and often fatal disease. When larger doses were used, chinchillas responded uniformly to the challenge. Although diarrhea was not evident, large amounts of fluid accumulated throughout the gastrointestinal tract. The severity of symptoms was related to the amount of fluid accumulated. The latter was directly proportional to the number of vibrios found in the small intestine at necropsy. Analysis of blood, serum, and intestinal fluid of collapsed, choleragen-inoculated chinchillas revealed that animals developed acute acidosis and dehydration manifested by hemoconcentration; intestinal fluid was isotonic to serum, rich in potassium, and almost free of proteins. Histologically, the intestinal mucosa appeared to be intact. Goblet cells were only infrequently encountered. Since the chinchilla is small, inexpensive, immunologically competent, and reproducibly susceptible to infection with V. cholerae, its use as an animal model in cholera research is suggested.