Using pancreactectomized (PX) dogs, we recently suggested the importance of glucagon in modulating amino acid-induced increases in renal blood flow (RBF) and glomerular filtration rate (GFR). We have now ascertained whether glucagon's modulatory effect is associated with an impairment in renal autoregulation. As renal arterial pressure (RAP) was reduced to 70 mmHg (the lower limit of the autoregulatory range) in both sham-operated control (C) and PX control dogs, RBF and GFR remained at values that were greater than 90% of their respective controls. In control dogs infused with amino acids (0.051 mmol/kg per min, i.v.), RBF and GFR rose by 26 and 27%, respectively, at baseline RAP. As RAP was reduced to 70 mmHg, RBF and GFR fell by 25 and 37%, respectively. In PX dogs infused with either amino acids or glucagon (0.86 pmol/kg per min, i.v.) alone, RBF and GFR did not increase appreciably at baseline RAP. As RAP was reduced to 70 mmHg in these dogs, RBF and GFR remained at values that were greater than 90% of their respective controls. Yet, in PX dogs infused simultaneously with amino acids and glucagon, RBF and GFR rose by 22 and 24%, respectively, at baseline RAP. Moreover, as RAP was reduced to 70 mmHg, RBF and GFR fell by 22 and 31%, respectively. These data suggest that the ability of glucagon to modulate the renal hemodynamic response to amino acid infusion involves an impairment in renal autoregulation.