Two experiments were carried out using adult castrated sheep prepared with jugular vein catheters. In Experiment 1, sheep (N = 8) were injected iv with saline vehicle, vehicle + 15 or 30 micrograms oCRH, or subjected to 120 min mild physical stress (restraint), following a 48 h period during which water was freely available or withheld. Blood samples were taken for 30 min before and 120 min after oCRH injection, and before and during restraint, and the plasma analysed for AVP and cortisol content. Levels of AVP increased by over 500% after dehydration, but were unaffected by oCRH or restraint. In contrast, plasma cortisol was unchanged after dehydration, but increased after oCRH and restraint. Moreover, these cortisol responses were significantly greater when the sheep were dehydrated. In Experiment 2, euhydrated sheep (N = 6) were infused iv with saline vehicle or vehicle + AVP for a 5-h pretreatment period, followed by a 2-h experimental period in which the animals were injected with 15 micrograms oCRH or subjected to 120 min restraint, as in Experiment 1. Blood samples were taken throughout the experiment from a contralateral catheter and the plasma analysed for AVP and cortisol content. The AVP infusion produced plasma levels of the hormone approximately twice those seen after 48 h dehydration in Experiment 1, but did not affect cortisol secretion. Furthermore, the cortisol response to oCRH, or restraint, was not enhanced by the AVP infusion. These results suggest that pituitary responsiveness to exogenous or endogenous CRH (restraint stress) may be enhanced in sheep by dehydration through a mechanism that does not involve an adrenal or pituitary action of circulating AVP.