We compared the 60-min splanchnic and renal hemodynamic responses to intraportal (IPV) and intravenous infusion of glucagon (5 ng.kg-1.min-1) in anesthetized dogs and quantitated the importance of glucose in mediating the renal hemodynamic responses to intraportal infusion of glucagon. Intraportal glucagon elevated superior mesenteric (SMA) and renal (RA) artery blood flows by 8 and 16%, respectively, by minute 15. By minute 30, RA flow had increased by 23%. Thereafter, SMA flow returned to control, while RA flow remained elevated by 24%. Glomerular filtration rate (GFR) followed the same pattern as RA flow over 60 min. Intravenous glucagon elicited smaller hemodynamic responses. During intraportal and intravenous glucagon infusion, plasma glucose rose by 20-25%. Renal hemodynamics were not affected by incremental changes in blood glucose of up to 6.25 mmol/l. At an incremental change in glucose of 10.06 mmol/l, RA flow and GFR were elevated by 12 and 9%, respectively. We conclude that intraportal glucagon infusion increases splanchnic and renal hemodynamics, although the splanchnic response is evanescent. Importantly, hepatic release of glucose into the circulation during intraportal glucagon infusion does not have a significant effect on renal hemodynamics. Thus, similar to intravenous infusion of the hormone, renal hemodynamic responses to intraportal glucagon are independent of and dissociated from elevations in blood glucose produced during hormone infusion.