The state of the art in insect allergy before 1973 consisted of obtaining a history, sometimes performing skin tests with one or more insect whole body extracts (WBEs), and, if convinced of the veracity of the history, treating the patient with WBE. Although some allergists, especially Dr. Mary Loveless, 1 challenged this practice and suggested that venom and not insect bodies contained the allergens, they were generally ignored for lack of convincing scientific evidence. A 4-year-old boy was seen at the allergy clinic of Johns Hopkins University in 1973 who had experienced 2 near fatal reactions to honeybee stings, the second following a course of WBE immunotherapy. His sister had previously died from bee sting anaphylaxis, and his father was a commercial beekeeper. Lichtenstein and colleagues 2 had the father collect bee venom and attempted rush desensitization. At the equivalent of 1/3 sting (15 ~g), systemic symptoms began and they became severe at a dose of 50 ~,g. The patient was placed on a slower injection protocol and eventually could tolerate 100 p,g. At this time serologic studies showed a substantial rise in IgG antibodies against venom and the patient tolerated an intentional sting challenge. This single case was the beginning of an extensive research program at Johns Hopkins University and other institutions, which led to controlled scientific studies of many of the variables in insect venom allergy and, ultimately, to the licensing of bee venom and vespid venom protein extracts for human use. Present standards for dose, regimen, and some of the indications for immunotherapy are based on controlled studies; but many questions are still unanswered, such as the ability to predict severe reactions in untreated individuals, cross-reactivity and multiple reactivity among the venoms, and the duration of immunotherapy. Venom allergy will be an active area of research for many years. The prevalence of severe reactions to insect stings is unknown. Studies performed mainly by tabulating questionnaires filled out by parents and phy