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During the past two years, six patients with systemic mastocytosis have required general or regional anesthesia for operative correction of various surgical problems. Mastocytosis constitutes an extremely difficult problem in diagnosis and management. A large experience with patients with mastocytosis in the Vanderbilt Medical Center in the last decade has enhanced awareness of this disorder and increased its early recognition. The hazardous problems of systemic mastocytosis and the difficulties of its diagnosis and management are summarized and focussed on the increased hazard of those patients with this disease who require various surgical operations. Close collaboration between anesthesiologists, surgeons, and internists in this medical center in the past two years has made it possible to carry six of these patients through anesthesia, operation, and the postoperative period safely and without fatality.