Three hundred twenty-four patients with a history of yellow jacket- (n = 272) or honeybee- (n = 52) sting anaphylaxis were prospectively subjected to an in-hospital sting challenge. Plasma levels of specific IgE and IgG4, skin venom tests, severity of previous reaction, sex, age, atopic constitution, histamine skin test results, location and number of previous stings, time interval between previous anaphylactic reaction and sting challenge, and time interval between sting challenge and onset of anaphylaxis were studied in relation to the clinical severity of a reaction after sting challenge. A recurrent anaphylactic reaction after sting challenge was observed in 25% of yellow jacket- and in 52% of honeybee-sensitive persons. The severity of this reaction correlated significantly with age and the time interval between sting challenge and onset of anaphylaxis only: older persons with faster reactions had more severe symptoms after sting challenge. None of the current criteria for insect-sting hypersensitivity (IgE, IgG4, skin test) significantly related on an individual basis or in combinations to the reaction after sting challenge. We conclude that the current criteria to assess insect-venom hypersensitivity do not relate to the occurrence and severity of anaphylactic symptoms after an insect-sting challenge.