In studies on seven anephric patients, glucose and insulin administration before hemodialysis produced a significant reduction in plasma potassium concentration (mean reduction = 1.3, 1.7, and 1.4 meq/liter at 60, 120, and 180 min, respectively) which was accompanied by a significant and sustained reduction in plasma aldosterone concentration. There was a significant correlation between plasma aldosterone and plasma potassium concentration (r = +0.74, P < 0.001) and between changes in the concentration of plasma aldosterone occurring in individual patients and the corresponding changes in plasma potassium concentration (r = +0.52, P < 0.01). There was no significant change in plasma sodium concentration, and plasma corticoid concentration, which was monitored as an index of ACTH elaboration, was reduced at 60 min but increased subsequently as symptoms attributable to hypoglycemia were observed. These studies demonstrate that plasma aldosterone concentration can be modulated acutely by transitory changes in plasma potassium concentration without a change in potassium balance. The effect of glucose and insulin administration on intracellular potassium in the adrenal cortex is uncertain, and although increased net movement of potassium into cells is the presumptive mechanism of the reduction in plasma potassium concentration, whether the potassium content of the adrenal cortex may have increased or decreased or remained essentially unchanged, cannot be inferred from our data.