The loss of normal villous architecture of the mucosa with some degree of flattening is a characteristic response of the small intestine to many forms of mucosal injury. Indeed, the height of the villi and the depth OF the crypts represent important markers for identifying morphologic abnormalities in the small intestine.* Nevertheless, little is known about the mechanisms of villous flattening or its reversal. Normally, a continuous, single layer of epithelium covers the villi and lines the crypts of the small intestine. Epithelial cell renewal occurs in the proliferative zone in the crypts where undifferentiated cells divide to provide a constant source of new cells which migrate toward the gut lumen and are extruded.’ Ci:ll migration time from crypt to villous tip in the human proximal small bowel is 5-6 days.” The paradigm of the flat villous lesion is that which occurs in gluten-sensitive enteropathy or celiac sprue.” The gluten-induced lesion results in damage to the surface epithelial cells, reducing their life span and increasing their shedding into the intestinal lumen. This results in eventual villous flattening with compensatory lengthening of the crypts.5-8 It is now well established that many disorders which result in surface epithelial cell damage lead to a lesion similar to that observed in gluten-sensitive enteropathy” (see Table 1). Some of these disorders are more prevalent in infancy and include: acute’” and chronic” infectious enteritis, cow’s milk protein sensitivity,12 soy protein enteropathy,13 eosinophilic gastroenteritis,“’ tropical sprue,l’ immunodeficiency syndromes,” collagenous or unclassified sprue,j7 malnutrition, most notably kwashiorkor,” bacterial overgrowth,” giardiasis,“” and dermatitis herpetiformis.” Villous shortening has also been reported in association with certain drugs” and radiation.23 Many of these conditions, unlike gluten-sensitive en-