The response of the rat proximal colon to an immunoglobulin E (IgE)-mediated hypersensitivity reaction was examined. Rats were sensitized to egg albumin (EA) by intraperitoneal injection, and serum titers of specific anti-EA IgE were measured at 14 days. Sensitized animals had titers of greater than or equal to 1:64, whereas no anti-EA IgE antibodies were detected in controls. Water and electrolyte absorption in the proximal colon, before and during antigen challenge, was measured by in vivo marker perfusion. Antigen challenge resulted in significant inhibition of water, Na+, Cl-, and K+ absorption in vivo. Proximal colonic tissue from sensitized and control animals was studied in Ussing chambers under short-circuited conditions. Antigen challenge of sensitized tissue resulted in significant increases in short-circuit current due to the induction of active Cl- secretion. No such changes were seen in control tissue. The abnormalities induced by antigen challenge in tissue from sensitized animals was blocked by doxantrazole (10(-3) M), a mast cell stabilizer. The findings indicate that IgE-mediated reactions in rat proximal colon to a food protein cause pertubations in water and electrolyte transport secondary to active Cl- secretion and these abnormalities appear to be due to mast cell degranulation.