The response of the jejunal villous epithelial cell and its subepithelial tissues to a single dose of gluten was studied with the electron microscope in 3 coeliac patients treated with a gluten-free diet for 3 years or more and compared with that of a non-coeliac child. Up to 48 h after gluten administration the epithelial cells of the coeliac patients showed no abnormality but the subepithelial basement membrane was thickened, the capillary endothelium showed swelling and there was an increased infiltration of lymphccytes, eosinophils and plasma cells in the intercellular and subepithelial spaces. Epithelial damage was seen at 96 h after gluten in only one of 2 patients. The ultrastructural changes in the non-coeliac child 24 h after gluten were entirely confined to the epithelial cell itself and consisted of large intracytoplasmic vacuoles, lined by smooth membranes which contained fibrous and other unidentifiable material. The absence of an intracellular reaction at least in the early stages following gluten in the coeliac patients could be due to an ineffectiveness in walling-off exogenous material such as gluten and may be of importance in allowing antigenic material to pass through the cell thus setting up immunological reactions in the subepithelial connective tissue and nearby capillary endothelium.