Anaphylactoid reactions to vancomycin have been reported consistently since the earliest clinical trials. Signs and symptoms of the reaction, which usually occur during the first dose, can range in severity from mild pruritus and upper body flushing, to dramatic hypotension and cardiovascular arrest. The frequency of the reaction, and its severity, is proportional to the total dose administered and the infusion rate. Recent prospective investigations report that when 1 g of vancomycin is administered over 60 min to normal volunteers and infected patients, between 50-90% of adults will have a reaction, although most are mild and of little clinical consequence. Vancomycin causes a release of histamine into blood, and the severity of the reaction is proportional to the amount of histamine released. Tachyphylaxis rapidly develops in most persons, although decreasing the dose, or increasing the infusion time will also help alleviate the signs and symptoms. Antihistamine H1 blocking agents are also effective in preventing the reaction. Teicoplanin, a new glycopeptide antibiotic, does not appear to cause histamine release or related symptoms, even when administered at a more rapid rate than vancomycin.