Acute, severe injury is frequently attended by hypotension, hypothermia, and decreased metabolic rate despite elevated urine and plasma catecholamine levels. Because the combination of sympathetic nervous system (SNS) suppression and adrenal medullary stimulation documented in several other situations could account for these observations, SNS and adrenal medullary function were examined independently in mice in the hindlimb ischemia model of acute injury. SNS activity was assessed by the measurement of [3H]norepinephrine (NE) turnover in heart and adrenal medullary secretion by depletion of adrenal catecholamine content. In nine separate experiments during the first 10 h after termination of a 2.5-h period of hindlimb ischemia, cardiac NE turnover was reduced an average of 23% (P less than 0.05) in injured mice. At the same time, adrenal catecholamine content fell 37% (P less than 0.05) in injured animals but not in controls. In contrast to the acute reaction, SNS activity in mice surviving 3 days was 59% greater than in controls. Thus, the reduction in NE turnover and depletion of adrenal catecholamine content suggest that SNS suppression and adrenal medullary stimulation constitute the acute sympathoadrenal response in this model of severe injury. Because survival within the first 24 h after injury was decreased in adrenalectomized mice despite glucocorticoid treatment, adrenal medullary catecholamines may contribute to survival in severely injured animals. Furthermore, because the SNS plays an important role in the regulation of blood pressure and heat production, the diminution in SNS activity in the hours after injury may contribute to posttraumatic hypotension and hypometabolism.