This study examined whether a mild inflammatory state induced by acetic acid would alter ovalbumin-induced motor and secretory responses of the actively sensitized colon. Short-circuit current (Isc), a measure of active transepithelial ion transport, and longitudinal contractility were measured, respectively, in mucosa-submucosa or smooth muscle sheets from guinea pig distal colon. Ovalbumin produced similar, concentration-dependent increases in Isc in noninflamed and inflamed colonic mucosa. Chlorpheniramine, an H1-histamine antagonist, produced a concentration-related decrease in antigen efficacy that was greater in noninflamed mucosa than in inflamed tissues. Lipoxygenase inhibitors (R840 and A64077) were equally effective in decreasing ovalbumin-induced secretion in both inflamed and noninflamed tissues. Ovalbumin also produced longitudinal muscle contractions that were of similar magnitude in inflamed and noninflamed strips. Moreover, chlorpheniramine and lipoxygenase inhibitors inhibited contractile responses in muscle from both inflamed and noninflamed colons. These results suggest that inflammation produces hyperresponsiveness in the colonic mucosa but not in the underlying longitudinal smooth muscle.