The effects of an acute protein load on renal hemodynamic responses and plasma glucagon levels were investigated in 31 patients with biopsy proven chronic glomerulonephritis (24 cases) or chronic renal failure (6 cases). After baseline clearance measurements, the subjects ingested a high protein meal consisting of 1.2 to 1.5 g protein/kg body weight in the form of cooked beef followed by a second set of measurements. This acute protein load resulted in a rise of both creatinine and PAH clearances (from 86.5 +/- 6.0 ml/min to 98.3 +/- 7.1 ml/min and 531.1 +/- 59.1 ml/min to 688.9 +/- 72.9 ml/min, respectively). This was associated with an elevation of plasma glucagon levels from 104.6 +/- 7.9 pg/ml to 134.5 +/- 7.5 pg/ml. From these data we suggest that the augmentation of renal function following a high protein intake may be mediated by the simultaneous rise of plasma glucagon levels, and that the glucagon concentration in the portal vein rather than in the peripheral blood has a pivotal role in this setting.