Both oral protein ingestion and intravenous amino acid infusions have been shown to increase glomerular filtration rate (GFR) and renal plasma flow (RPF) in normal subjects. Although the mechanism of this effect is not known, the renal responses to these loads have been associated with increases in peripheral glucagon concentrations. Conflicting data exist concerning the role of glucagon in the hyperfiltration response after an oral protein meal or administration of an intravenous amino acid mixture. Using a single amino acid as the stimulus for hyperfiltration, we compared the renal responses in six normal subjects to 30 gm oral arginine-HCl, intravenous arginine-HCl, and intravenous glucagon infused at the rate of 10 ng/kg/min. GFR, RPF, and glucagon concentration, as well as levels of plasma amino acids and selected gastrointestinal hormones, were measured for six 30-minute clearance periods after each load. Significant rises in mean peak GFR were noted after both oral arginine (104 +/- 5 ml/min x 1.73 m2 to 145 +/- 9 ml/min x 1.73 m2, p less than 0.02) and intravenous arginine (118 +/- 10 ml/min x 1.73 m2 to 134 +/- 11 ml/min x 1.73 m2, p = 0.02) administration. Mean peak RPF rose significantly after oral arginine (510 +/- 26 ml/min x 1.73 m2 to 710 +/- 32 ml/min x 1.73 m2, p less than 0.01) but not after intravenous arginine (616 +/- 60 ml/min x 1.73 m2 to 687 +/- 64 ml/min x 1.73 m2, p = 0.18). Intravenous glucagon infusion also increased both mean peak GFR (99 +/- 9 ml/min x 1.73 m2 to 149 +/- 10 ml/min x 1.73 m2, p less than 0.01) and RPF (514 +/- 48 ml/min x 1.73 m2 to 771 +/- 38 ml/min x 1.73 m2, p less than 0.01) significantly. We found the mean peak percent rise in GFR (43% +/- 13%) and RPF (42% +/- 12%) after oral arginine to be notably greater than that after intravenous arginine (14% +/- 5% and 13% +/- 9%, respectively). However, the mean peak percent rise in glucagon concentration after oral arginine was significantly lower than that after intravenous arginine (62% +/- 25% versus 479% +/- 176%, respectively, p = 0.04). Infusion of glucagon increased GFR (54% +/- 13%) and RPF (55% +/- 12%) to a degree similar to that seen after oral arginine, but again with a significantly higher mean peak percent rise in peripheral glucagon concentrations when compared with the rise after oral arginine (798% +/- 348% vs 62% +/- 25%, p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)