Introduction The natural history of stings, the clinical reaction of the patient and in vivo and in vitro tests are necessary parameters to assess before initiating Hymenoptera venom immunotherapy. In the decision to initiate immunotherapy with Hymenoptera venom, it is not usual to evaluate the natural history of the disease, which seems to be self‐limiting and therefore of variable clinical significance.

Objectives Our aim was to determine the natural history of Hymenoptera hypersensitivity over 4 consecutive years in a rural Mediterranean population.

Methods An epidemiological study of Hymenoptera sting reactions and possible sensitivity was carried out in 145 randomly selected subjects out of a rural Mediterranean population of 600. Seventy‐two subjects, including those with a history of anaphylaxis, completed the 4‐year study. The nature of their clinical reactions, age, sex, history of atopy, profession, family history of reactions to Hymenoptera insects, time elapsed since the last sting, number of stings and specific IgE and IgG were determined (the latter, to the three most important insects in the area: Apis mellifera, Polistes dominulus, and Vespula germanica).

Results Of the 72 subjects, four subjects had systemic reactions (SR), 23 had large local reaction (LLR) and all the others (117) was minor local reactions. None who had experienced an SR had a repeat SR when re‐stung over the 4‐year study. Of those with LLR, 12 subjects had the same type of reaction and 11 experienced more mild local reactions when re‐stung. In the SR and local reaction groups, IgE to honey bee (Hb) increased significantly during the study period, whereas in those with only LLR, specific IgE to wasp (Polistes) decreased. Specific IgG to Polistes and Vespula (wasps) decreased significantly, whereas there was no change in the specific IgG to Hb in any of the groups. The number of stings per year decreased at the end of the study in all groups, but positive‐specific IgG was higher in subjects with the greatest number of stings. On multivariate analysis using logistic regression, the existence of specific IgE to bee venom, male sex, being an agricultural worker, age of over 16 years and more than five stings per year are seen as individual or co‐factors for developing SR or LLR.

Conclusions The prevalence of SR was 2.8% in our Mediterranean population. The evolution of IgE and IgG throughout the 4‐year study differed depending on the Hymenoptera studied. Adult male agricultural workers are at greater risk of having SR or LLR, especially when they have specific IgE to Hb and suffer from more than five stings every 4 years.