Potassium depletion of various causes has been shown to be associated with impaired carbohydrate metabolism. Abnormal carbohydrate tolerance developing during thiazide diuretic administration has been found to be reversible upon potassium replenishment, implying that this abnormality is a consequence of potassium depletion. Severe potassium depletion, hypokalemia and abnormal carbohydrate tolerance tests were observed in a patient given chlorthalidone. Oral potassium supplementation resulted in restoration of normokalemia and a return to normal of glucose tolerance. Plasma insulin response to oral glucose or intravenous tolbutamide was distinctly enhanced upon potassium replenishment. These studies suggest that the effect of potassium depletion on carbohydrate metabolism is mediated via an impairment of plasma insulin response to appropriate stimuli. 1 This study was supported by grants (AM-08106,TO 1-AM 05338, FR 05503) and a Research Career Development Award (KO 3-AM-13767 (S.J.B.) from the National Institutes of Health, Bethesda, Maryland.