We studied the influence of sex on the adrenal catecholamine response to acute insulin-induced hypoglycemia in Sprague-Dawley rats. Eight male and seven female adult rats were anesthetized with pentobarbital, and a microdialysis probe was placed in the left adrenal. Dialyzed epinephrine and norepinephrine levels were measured by high-performance liquid chromatography during a control period and for 1 hour after insulin administration. The blood glucose level was measured every 15 minutes. The same protocol was applied to 23 adult females at various stages of the estrus cycle. The pattern of blood glucose changes during insulin-induced hypoglycemia was similar in both sexes, but males exhibited a significantly greater increase in epinephrine than females (261% v 52%, P = .001) in the sex-comparison experiment. A similar trend was observed for norepinephrine (73% v 0%, P = .075). The adrenal response in females for both catecholamines was not significantly affected by the estrus cycle phase (P = .989 for epinephrine and P = .424 for norepinephrine). We conclude that sex influences the magnitude of the adrenal catecholamine counterregulatory response to hypoglycemia. Males had a significantly greater increase in epinephrine release than females exposed to the same pattern of hypoglycemia. Female responses to hypoglycemia were not influenced by estrus cyclicity.