The neuroendocrine hormones adrenocorticotrophic hormone (ACTH) and corticotrophin-releasing factor (CRF), which are involved in the stress response, have acute effects on arterial pressure. New evidence indicates that urocortin (UCN), the putative agonist for the CRF type 2 receptor, has selective cardiovascular actions. The responses to long-term infusions of these hormones, both peripherally and centrally, in conscious animals have not been studied. Knowledge of the long-term effects is important as they may differ considerably from their acute actions and stress is frequently a chronic stimulus. The present experiments investigated the cardiovascular effects of CRF, UCN and ACTH in conscious sheep. Infusions were made either into the lateral cerebral ventricles (ICV) or intravenously (IV) over 4 days at 5 µg/h. UCN infused ICV or IV caused a prolonged increase in heart rate (HR) (P's<0.01) and a small increase in mean arterial pressure (MAP) (P's<0.05). CRF infused ICV or IV progressively increased MAP (P's<0.05) but had no effect on HR. Central administration of ACTH had no effect, whereas systemic infusion increased MAP and HR (P's<0.001). In conclusion, long-term administration of these three peptides associated with the stress response had prolonged, selective cardiovascular actions. The striking finding was the large and sustained increase in HR with ICV and IV infusions of UCN. These responses are probably mediated by CRF type-2 receptors, as they were not reproduced by infusions of CRF.