No clear criteria exist to rule out hypoadrenal shock by cosyntropin (alpha 1-24-corticotropin, a synthetic subunit of adrenocorticotropic hormone) testing in persons who have critical nonadrenal illness. Four patients in the surgical intensive care unit with critical multisystem disease and refractory high cardiac output, low vascular resistance shock had significantly diminished or terminated vasopressor requirements after institution of hydrocortisone sodium succinate infusion in doses simulating physiologic stress response (100 to 300 mg of hydrocortisone per day). In each case, cosyntropin testing revealed serum cortisol levels higher than those usually associated with hypoadrenal shock. Positive response was defined as maintenance of blood pressure with a decrease to less than 25% of baseline pressor requirements within 48 hours of treatment. We hypothesize a syndrome of functional hypoadrenalism in patients with multisystem critical illness and refractory shock responsive to glucocorticoid administration in doses simulating physiologic stress response despite cosyntropin stimulation test results that would rule out hypoadrenalism in a normal person.