Sprague-Dawley rats were exposed to lectins, either concanavalin A (Con A) or wheat germ agglutinin (WGA). The lectins were instilled into a ligated segment of the distal small intestine together with permeability markers, fluoresceinated dextran (MW 3,000) or a mixture of differently sized polyethylene glycols (MW 400, 600 and 1,000). WGA-treated rats showed a decreased permeability to small molecules (MW less than 600) of polyethylene glycol but an increase for a larger dextran molecule (MW 3,000). These effects as well as the morphological findings might mimic the situation in patients with food allergy or celiac disease. Con A-treated rats had decreased intestinal permeability to the larger dextran molecules (MW 3,000), whereas the passage of small molecules was unaffected and the ultrastructural effects were minute. The Con A-induced changes could result from a mucotractive effect, associated with a low-grade gut allergy. These observations suggest that lectins can affect both the ultrastructure and the permeability of the intestine, in a way assumed to mimic allergic reactions to food constituents.