We examined the ability of physiological hyperinsulinemia to enhance potassium and glucose uptake by splanchnic and peripheral tissues in 12 chronically uremic subjects by using the euglycemic insulin clamp technique in combination with hepatic and femoral venous catheterization. In control subjects, the decline in plasma potassium concentration averaged 0.95 +/- 0.05 meq/liter. Splanchnic (67 +/- 10.3 mu eq/min) and leg (22.2 +/- 1.4 mu eq/min) potassium uptake accounted for 43 and 59%, respectively, of the total amount of potassium that was translocated from the extracellular to intracellular fluid compartment. In uremic individuals, the decline in plasma potassium concentration (0.98 +/- 0.10) was similar to controls. Likewise, the mean splanchnic (66.6 +/- 6.1 mu eq/min) and leg (22.4 +/- 1.6 mu eq/min) potassium uptakes were similar to controls. These results indicate that insulin-mediated potassium uptake is not altered by uremia. In contrast, insulin-mediated glucose uptake is markedly impaired. These observations suggest that the various actions of insulin can be differentially impaired by uremia and that steps distal to the insulin receptor must be responsible for the insulin resistance.