Although a variety of plant lectins are consumed as part of the normal human diet and are capable of binding to intestinal cell surfaces in vitro, little information exists on their effects on intact intestine. We have studied the acute effects of intraluminal administration of wheat germ agglutinin and concanavalin A in normal rats. Both lectins caused increased shedding of brush border membrane and, at higher concentrations, reduction in surface area, acceleration of cell loss, and shortening of villi. These changes were prevented by simultaneous administration of the appropriate sugar to inhibit binding, indicating that the effects were related to binding to carbohydrate residues of intestinal cells. Similar changes of brush borders were found after intraluminal administration of antiserum to sucrase-isomaltase, a surface protein of the brush border membrane, suggesting that the lectin effects resulted from cell surface receptor-lectin interaction rather than a primary intracellular effect. Our results suggest that dietary lectins may be in part responsible for normal turnover of brush border membrane, and support, in addition, the possibility that certain intestinal diseases such as celiac sprue may be the consequence of increased levels of lectin receptor allowing a dietary lectin to exert a toxic effect.