Epithelium of isolated small intestinal segments were studied in Ussing-type chambers to detect physiological changes associated with rapid, immune rejection of Trichinella spiralis infective larvae. Electrophysiological parameters associated with Na+-coupled hexose transport were measured. Changes in transepithelial electrical potential difference (PD), resistance, and short circuit current (Isc) due to the addition of actively absorbed beta-methyl-D-glucoside (BMG) to the mucosal solution were determined. Measurements were made prior to and 30 min after primary and secondary infections. Animals were infected by intraduodenal inoculation. As the infective larval dose in primarily infected (nonimmunized) rats increased from 50 to 2000 larvae the magnitude of the rise in Isc elicited by BMG decreased in a dose-dependent fashion, with 50 larvae per rat having no effect. In previously infected (immunized) rats challenged with a secondary inoculum, all doses, ranging from 50 to 2000 larvae per rat, decreased the BMG-stimulated change in Isc by approximately 50%. The effect of 50 worms per rat in immunized hosts was equivalent to that produced by approximately 1600 worms in nonimmunized animals. Measurements of 14C-BMG mucosa-to-serosa flux confirmed that Na+-BMG cotransport was responsible for observed changes in Isc. Results support the conclusion that changes in intestinal epithelial function are associated with larval challenge of immune rats.