Severe short-term sodium restriction or extreme sodium loading may alter glucose tolerance and insulin resistance in patients with hypertension, but it is unclear whether variations in sodium intake within the clinically observed range affect glucose tolerance. To examine this issue, 21 patients with primary hypertension with average sodium excretion of 116+/-55 mEq/day were randomized to consecutive 4-week periods of placebo therapy and sodium chloride supplementation 2 g four times a day in a single-blind crossover study design. A 75-g oral glucose tolerance test (GTT) with simultaneous insulin levels was performed at the end of each intervention period. For the group as a whole, urinary sodium excretion increased on sodium chloride to 267+/-118 mEq/day versus control (placebo) phase of 135+/-53 mEq/day, P < .001. Total glycemic response in the oral GTT (area under the glucose curve) was 8.0% lower during sodium supplementation, P < .001. Secondary analysis revealed that the effect of sodium was noteworthy in 1) type 2 diabetic subjects (n = 8), 2) sodium-sensitive subjects (n = 10), and 3) nondiabetic subjects receiving antihypertensive drug treatment (n = 6). The total insulinemic response to oral GTT was also lowered by sodium loading among diabetic subjects. Thus, an abundant sodium intake may improve glucose tolerance and insulin resistance, especially in diabetic, salt-sensitive, and or medicated essential hypertensive subjects.