Kallikrein and bradykinin additively increased adipocyte hexose transport under conditions of maximal intrinsic insulin stimulation, while no such effect occurred in the absence of insulin. The potentiation of insulin action follows a dose-response relationship with kallikrein and bradykinin concentrations consistent with a physiological role for the latter in the modulation of insulin action. Insulin degradation by isolated adipocytes and insulin binding to its receptors on adipocyte plasma membranes were not affected by either kallikrein or bradykinin. Thus, the kallikrein and bradykinin potentiation of insulin action occur at post-insulin binding sites. In conclusion, the kallikrein-bradykinin system increases the supply of substrates to target tissues through vasodilation and augmented blood perfusion, and it also stimulates glucose uptake and metabolism via its potentiation of insulin action. These actions suggest that the kallikrein-bradykinin system regulate both the availability and utilization of metabolic substrates, in target tissues.