The ultrastructural effects of 11 lectins on the intestinal brush border were examined by means of an in vitro rabbit ileal mucosal explant culture system. Five of the lectins that bind to oligosaccharides containing either N-acetylglucosamine (phytohaemagglutinin, Euonymus europaeus lectin, pokeweed mitogen, and wheat germ agglutinin) or N-acetylneuraminic acid (Mycoplasma gallisepticum lectin) all had a specific effect on microvilli. The effects varied in accordance with the lectin and included lengthening, distortion, and vesiculation of the microvilli. In contrast, lectins binding specifically to galactose, glucose, mannose, and N-acetylgalactosamine had no effect. Incubation of mucosal fragments with the divalent cation ionophore A23187 did not mimic the effect of the lectins. This apparent relationship between lectin damage and receptor specificity may reflect either accessibility of appropriate binding sites or a differential response to binding.