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Catecholamine-induced desensitization of β-adrenergic receptors resulting in hyporesponsivness to further stimulation has been frequently reported after an increase in endogenous catecholamines. To examine the possibility of β-adrenoceptor desensitization due to intraoperative adrenergic activation (surgical stress), the alterations of human lymphocyte β-adrenergic receptor density and affinity observed after anesthesia and surgery Were studied using (−)251I-iodocyanopilldolol binding in 19 Patients Undergoing noncardiac surgical procedures with general anesthesia (thiopental, fentanyl, and halothane or isoflurane). In 13 patients, repeated determinations of plasma levels of norepinephrine and epinephrine showed an increase during the surgical procedure (norepinephrine ±60%; epinephrine +60%); this change was not observed in the remaining patients. A significant postoperative increase in receptor density (Bmax +25%) and a significant decrease of receptor affinity for isoproterenol (IC50 +22%) were found in the patients who experienced intraoperative adrenergic activation. By contrast, no significant change in β-receptor density or affinity was found in the patients who had normal intraoperative adrenergic activation. In addition, heart rate responses to the postoperative changes in plasma catecholamines (an index of cardiac sensitivity to agonist) were significantly attenuated in patients who experienced both intraoperative adrenergic activation and a decrease in affinity of β-receptor for agonist, suggesting hyporesponsiveness to β stimulation. We conclude that β-adrenergic receptors and, consequently, β-adrenergic responsiveness might be altered by perioperative adrenergic activation in surgical patients.