Acute stress increases ion secretion and permeability of rat colonic epithelium. However, it is not known if stress-induced mucosal changes are subject to adaptation. Wistar-Kyoto rats were exposed to either continuous water-avoidance stress (CS) for 60 min or intermittent stress (IS) for three 20-min periods. Distal colonic segments were mounted in Ussing Chambers, and ion-transport [short-circuit current (I(sc))] and permeability [conductance and flux of horseradish peroxidase (HRP)] parameters were measured. CS significantly increased I(sc), conductance, and HRP flux compared with control values. In contrast, in IS rats these variables were similar to those in nonstressed controls. To study the pathways involved in IS-induced adaptation, rats were pretreated intraperitoneally with the opioid antagonists naloxone or methylnaloxone. Opioid antagonists had no effect on values in control or CS rats. However, in the IS group, naloxone and methylnaloxone reversed the adaptive responses, and all variables increased to CS values. We conclude that stress-induced colonic mucosal pathophysiology is subject to rapid adaptation, which involves opioid pathways.