Our results as well as those in the literature suggest that some hormone or combination of hormones, that are inhibited by somatostatin, is responsible for the hyperfiltration response following amino acid infusion/protein ingestion. Recently, we have infused amino acids with somatostatin and replaced the stimulated levels of insulin/glucagon/growth hormone observed during amino acid infusion alone (Castellino and DeFronzo, preliminary results). This combined hormone replacement was able to overcome the inhibitory effect of somatostatin and return the increase in RPF and GFR to the elevated levels observed following amino acid infusion. These results suggest that some combination of these hormones is involved in the hyperfiltration response to hyperaminoacidemia. However, several comments are worthy of emphasis. First, somatostatin is known to inhibit a number of hormones (Table 1), and a contributory role for any of these should not be excluded. Second, a large body of evidence has accumulated to indicate that neither insulin, glucagon, nor growth hormone alone are capable of augmenting either RPF or GFR. The possibility that infusion of the three hormones together will increase RPF and GFR, when neither hormone alone will do so, has not been examined. More likely, some interaction between the elevated plasma amino acid concentrations and the elevated hormone levels is responsible for the hyperfiltration response. It is interesting to speculate that such an interaction might be exerted at the level of the kidney by an effect on renal amino acid metabolism.