Potentiated adrenal responses to the second of two identical hemorrhages spaced 24 h apart are seen in the pentobarbital sodium-anesthetized dog. Although pentobarbital effectively reduces environmental influences, barbiturates affect hemodynamic and hormonal responses and preclude normal daily feeding and activity patterns. To determine the role of anesthesia in these earlier results, we prepared awake trained dogs with chronic adrenal venous catheters. Animals were bled 8.7-21.8% of measured blood volume [131] over 3 min, and peripheral and adrenal blood was sampled. Blood was reinfused 1 h later, and the dogs were fed. The protocol was repeated 24 h later. Dogs with small hemorrhage (11.6 +/- 2.3% blood vol; n = 9) showed no difference in catecholamine secretion on the 2 days. Dogs with large hemorrhage (18.9 +/- 2.1% blood vol; n = 9) showed a greater epinephrine and norepinephrine secretory response to hemorrhage on day 2. No differences were detected in the hemodynamic response to bleeding on the 2 days. Whereas potentiation was seen in epinephrine and norepinephrine responses to a second 10% hemorrhage in anesthetized dogs, larger hemorrhage was needed to elicit this effect in awake dogs. Thus potential adrenal medullary responses to repeated hemorrhage occur in both awake and pentobarbital-anesthetized dogs, but important differences in the threshold and manifestation of this effect are seen.