Effects of kappa opioid agonist, ketocyclazocine (KCZ) and its antagonist, M(r) 2266, were evaluated on some stress responses in rats. KCZ (1 or 10 mg/kg, ip) dose-dependently attenuated cold restraint stress (CRS)-induced gastric ulcer formation. Similar gastric cytoprotection was also seen with KCZ (1 or 10 micrograms/rat, icv). Pretreatment of rats with M(r) 2266 (0.3 mg/kg, ip) clearly antagonized the ulceroprotective effects of both ip and icv KCZ. KCZ effects on the gastric mucosa during CRS were also reduced by naltrexone (5 mg/kg, ip) pretreatment. KCZ (1 or 10 mg/kg, ip) also attenuated the plasma corticosterone response to CRS and these effects were blocked by M(r) 2266 (0.3 mg/kg) pretreatment. These results indicate kappa opioid receptor involvement during stress reactions and also suggest possible opioidergic interactions during CRS.