Indications for the administration of vancomycin in the perioperative period have expanded in recent years. Used in this situation, vancomycin has caused adverse reactions, the most serious of which is hypotension. We describe five patients who had adverse reactions to vancomycin perioperatively. Vancomycin-induced hypotension usually results from a negative inotropic and vasodilator effect produced in part by a histamine-release phenomenon, which occurs most commonly with rapid intravenous infusion of the drug. Such a release of histamine may also produce an acute urticarial flushing of the upper torso (the "red neck syndrome") and symptoms of pain and muscle spasm in the chest or paraspinal muscles, which may mimic myocardial infarction. These effects usually abate promptly when the infusion of vancomycin is discontinued, and their resolution may be expedited by administration of an antihistamine.