Effects of intravenous arginine and cholecystokinin-pancreozymin (CCK-PZ) infusion on hepatic extraction of insulin (EI) and glucagon (EGG) and also on hepatic glucose output (HGO) were studied in anesthetized dogs. Because insulin and glucagon exert antagonistic effects on HGO, insulin:glucagon (I/GG) molar ratios were determined in the portal vein and also in peripheral vessels. During the arginine-CCK-PZ infusion the amount of insulin and glucagon coming to the liver increased 12- and 15-fold, respectively. In contrast EI decreased significantly from a control value of 62 +/- 6% to a nadir of 22 +/- 13%. EGG (control value 19 +/- 9%), however, was unaffected by arginine-CCK-PZ. The absence of any alteration in EGG cannot be attributed to the molecular heterogeneity of the immunoreactive glucagon. HGO increased fourfold in response to the pancreatic stimulation, whereas portal I/GG decreased significantly from 8.2 +/- 0.9 to 5.0 +/- 0.7. The concurrent femoral arterial I/GG (control 3.7 +/- 1.0) and mesenteric venous I/GG (control 2.1 +/- 0.5) increased significantly. These observations indicate that portal, but not peripheral, I/GG measurements reflect hepatic events in anesthetized dogs, probably because of the different extraction patterns for insulin and glucagon.