Glucagon has been implicated in the hormonal-metabolic response to injury and in the restitution of blood volume. Evidence for this has been obtained largely from observations of peripheral glucagon concentrations. The secretory response to mild or moderate hemorrhage remains undefined. Experiments have been conducted in conscious dogs surgically prepared with indwelling catheters in the portal vein (PV), femoral artery (FA), and femoral vein (FV). In addition, electromagnetic flow probes were placed about the PV and the hepatic artery (HA). Animals were subsequently subjected to either a 10% (7.5 ml/kg), 20% (15 ml/kg), or 30% (22.5 ml/kg) 3-min hemorrhage. The portal venous delivery rate (PVDR) of immunoreactive plasma glucagon (IRG), portal venous IRG concentrtion (PVIRG), and peripheral arterial IRG (AIRG) demonstrated variable changes following hemorrhage. When hemorrhage resulted in marked deterioration in PVBF, then PVDR did not correlate with either changes in PVIRG or AIRG. These preliminary results suggest that inferences regarding changes in PVDR of IRG cannot reliably be based solely on changes in hormonal concentrations, especially when measured only in the periphery. Moreover, since marked increases in peripheral plasma glucose levels were observed at times when PVDR of IRG was severely depressed following 20% and 30% hemorrhage it is suggested that glucagon may not play the dominant role in the early hyperglycemic response to hemorrhage.