Background: Imported fire ants are a common cause of insect venom hypersensitivity in the Southeastern United States. Objective: The purpose of this study was to determine the most frequent insect cause for evaluation in a Hymenoptera hypersensitivity clinic in an area endemic for the imported fire ants. Methods: This was a retrospective study reviewing all patients seen in a venom clinic at a large teaching hospital. Results: Of the 703 patients evaluated, between 1985 and 1995, 515 (73%) had reactions consistent with systemic anaphylaxis for which a determination of specific IgE was appropriate. Of the 703 patients seen, 315 (45%) had a positive history and skin test positivity and were offered specific immunotherapy. This was 61% of those individuals skin tested. Of the total patients seen, imported fire ants were responsible for 42% of the visits to the clinic and accounted for 59% of the total immunotherapy that was begun in this endemic area. Conclusion: In areas endemic for the imported fire ants, the most frequent cause of Hymenoptera hypersensitivity is the imported fire ant.