Clostridium difficilecolitis is a disabling complication in critically ill patients who commonly receive broad‐spectrum antibiotics and liquid diets. To date, there is no experimental model specifically designed to investigate the effects of liquid diets on this type of colitis. The addition of fiber to liquid diets normalizes gut structure and improves absorptive function in selected conditions of intestinal dysfunction. The purposes of this study were the following: (1) to develop a reproducible model to examine the interaction of acuteC difficile‐induced colitis and liquid diets, (2) to determine whether the addition of soy fiber to a liquid diet improves disease, and (3) to investigate possible mechanisms of fiber‐mediated disease improvement. Syrian hamsters were pair‐fed with either a polymeric liquid diet or the same diet with 1.4% soy fiber for 10 days. Animals were given either clindamycin andC difficile(to produce ileocecitis), or equivalent volumes of saline. Mean survival time and systematic stool examinations forC difficiletoxin positivity, liquidity, and percent water were performed to determine the effect of soy fiber on disease. Survival time was prolonged by 34% (p<.05), andC difficiletoxin positivity and stool liquidity were significantly reduced (p<.05) with fiber. Additional animals were studied to determine possible mechanisms for improved survival in fiber‐supplemented animals. Cecal histology, colonic water absorption, cecal microflora, and gastric to anus transit time were measured in these animals. Colonic water absorption and gastric to anus transit time were significantly increased (p<.05) and decreased (p<.05) with fiber, respectively. A hamster model ofC difficileileocecitis has been designed to investigate the effects of liquid diets. Fiber supplementation prolongs survival in this model due in part to a delay in onset of C difficile infection and improved colonic water absorption. (Journal of Parenteral and Enteral Nutrition18:55–61, 1994)