In order to investigate the renal effects of amino acids (AA) with different metabolic fate, we compared the changes in glomerular and tubular function, nitrogen metabolism and glucoregulatory hormones in 7 volunteers during two infusions, one of a complete solution of amino acids (MIX-AA), which included five AA electively metabolized at the splanchnic level, and the other of a solution containing only essential AA (EAA), which escape splanchnic metabolism. MIX-AA increased GFR and RPF (from 104 +/- 6 to 122 +/- 13 and from 488 +/- 46 to 572 +/- 34 ml/min/1.73 m2), stimulated splanchnic metabolism as demonstrated by rises in urinary urea excretion (from 20.7 +/- 2 to 30.6 +/- 7.5 mg/min/1.73 m2) and the plasma glucagon/insulin ratio (from 21.4 +/- 13 to 26.7 +/- 15), and caused increases in fractional excretion of AA, FeNa and free-water clearance. During MIX-AA infusion significant correlations were observed between the individual values of GFR and the urea excretion rate (r = 0.66), and between GFR modifications (DeltaGFR) and the plasma glucagon/plasma insulin ratio (r = 0.40). No change in renal function, urea excretion and the glucagon/insulin ratio was observed with EAA. An intermediate splanchnic step (increased plasma glucagon/insulin ratio and ureagenesis) seems necessary in the pathway leading to the nonessential AA-induced rise in GFR; this might stimulate an ultimate intrarenal pathway (possibly involving the diluting segment) via a still undefined mechanism.