After an initial compensatory phase hemorrhage reduces blood pressure due to a widespread reduction of sympathetic nerve activity (decompensatory phase). Here we investigate the influence of intracerebroventricular (ICV) naloxone (opioid-receptor antagonist) and morphine (opioid-receptor agonist) on the two phases of hemorrhage, central and peripheral hemodynamics and release of vasopressin and renin in chronically instrumented conscious sheep. Adult ewes were bled (0.7 ml/kg/min) from a jugular vein until mean arterial blood pressure (MAP) reached 50 mmHg. Starting 30 min before and continuing until 60 min after hemorrhage either artificial cerebrospinal fluid (aCSF), naloxone or morphine was infused ICV. Naloxone (200 µg/min but not 20 or 2.0 µg/min) significantly increased the hemorrhage volume compared to aCSF (19.5±3.2 vs 13.9±1.1 ml/kg). Naloxone also increased heart rate and cardiac index. Morphine (2.0 µg/min) increased femoral blood flow and decreased hemorrhage volume needed to reduce MAP to 50 mmHg (8.9±1.5 vs 13.9±1.1 ml/kg). The effects of morphine were abolished by naloxone at 20 µg/min. It is concluded that the commencement of the decompensatory phase of hemorrhage in conscious sheep involves endogenous activation of central opioid receptors. The effective dose of morphine most likely activated µ-opioid receptors but they appear not to have been responsible for initiating decompensation since a) naloxone only inhibited an endogenous mechanism at a dose much higher than the effective dose of morphine, b) the effects of morphine was blocked by a dose of naloxone which by itself did not delay the decompensatory phase.