Recent studies in female mice that cannot synthesize oxytocin (OT) suggest that central OT neural pathways attenuate the response of the hypothalamic-pituitary-adrenal (HPA) axis to certain stressors. OT deficient (OT-/-) female mice had higher plasma corticosterone concentrations than wild type (OT+/+) female mice following exposure to platform shaker (Mantella et al., 2004). The present study examined the corticosterone response of OT-/- and OT+/+ male mice that were exposed to shaker stress or other stressors (i.e., administration of cholecystokinin (CCK), dehydration, or fasting) that are known to activate central OT neurons in mice. Plasma corticosterone concentrations were higher in male mice receiving each stress than in male mice not exposed to a stressor. Plasma corticosterone concentrations were higher in OT-/- than OT+/+ male mice that were water deprived (P < 0.05) or fasted (P < 0.03), whereas corticosterone concentrations following exposure to platform shaker or CCK administration (10 microg/kg i.p.) were not different between genotypes. These findings support the hypothesis that absence of OT results in a heightened response of the HPA axis to certain stressors and that OT can attenuate the corticosterone response associated with overnight food or water deprivation in male mice.