Systemic anaphylaxis is an acute allergic emergency resulting from generalized mast cell degranulation. In the United States, it is estimated that anaphylaxis accounts for about 500 deaths each year. Hymenoptera-sting hypersensitivity is one of the most common causes of systemic anaphylaxis. The authors report a case of a healthy 26-year-old man who developed acute anaphylaxis after a bee sting, could not be resuscitated, and died within 1 hour. At autopsy, performed 14 hours after the event, the only pathologic findings were laryngeal edema and congestion of lung. Postmortem tryptase levels in the blood were obtained and were instrumental in confirming a diagnosis of acute anaphylaxis. This case is reported to discuss the difficulties associated with using traditional histamine levels in making a diagnosis of anaphylaxis and to validate the value of using tryptase levels to document acute anaphylaxis as a cause of death, even when serum is not obtained until many hours after death.