The effect of chronic dietary antigen challenge on the intestine was examined in sensitized rats. Three groups of Hooded-Lister rats were studied: animals sensitized to egg albumin; sham-sensitized animals; and unmanipulated controls. In sensitized rats, serum immunoglobulin E titers to egg albumin were greater than or equal to 1:64, whereas control and pair-fed rats showed no response. Sensitized rats received egg albumin 1 mg/ml in drinking water and rat chow ad libitum. Pair-fed animals also received egg albumin but were pair-fed with sensitized animals. Controls received water and rat chow ad libitum. Chronic antigen challenge resulted in reduced food intake and weight gain in sensitized animals. When the rats were killed after 9 days of antigen exposure, proximal intestine from experimental animals showed decreased disaccharidase activity, brush-border microvillus surface, area, and villus height. Crypt depth and enterocyte migration rate were increased. Mucosal mast cell involvement was suggested by mast cell proliferation, evidence of mast cell degranulation, and increased serum rat mast cell protease II levels. At the time of death, only sensitized jejunum demonstrated an increase in short-circuit current in Ussing chambers in response to antigen challenge. The findings indicate that chronic antigen exposure leads to intestinal injury, reduced food intake, and diminished weight gain.