The endocrine response is an important component of the physiological response to blood loss. There is some variability in reported levels of certain hormones during hemorrhage such as the stress hormone adrenocorticotrophic hormone ( ACTH). Therefore, the effect of two anesthetic agents, ketamine and saffan, on ACTH and beta-endorphin levels during hemorrhage was assessed in 12 minipigs. The animals were divided into two groups, group I saffan and group II ketamine (n=6). Pigs were subjected to a continuous fixed volume hemorrhage under one of the above anesthetics while spontaneously breathing. Blood pressure and heart rate responses were recorded together with beta-endorphin and ACTH levels both before and at 10, 20, 30, 40 min after the onset of bleeding. ACTH levels were higher in the ketamine-anesthetized pigs and rose significantly faster with falling blood pressure than ACTH measured in pigs under saffan anesthesia. In contrast, the hemorrhage induced beta-endorphin increase was not significantly different between the two anesthetic groups. These results indicate that choice of anesthetic agent is important when investigating the hormone response to hemorrhage and may account for the variable hormone levels in the published literature to date.