Background: Anaphylaxis to fire ant venoms (Solenopsis sp) is a significant cause of systemic reaction caused by Hymenoptera stings in children. There are only a few reports about the safety and efficacy of specific immunotherapy. Objective: Evaluate clinical characteristics, IgE and IgG4 specific responses of patients undergoing immunotherapy with a whole-body extract of Solenopsis sp after one year of the maintenance phase. Materials and methods: Thirty-three patients were enrolled due to anaphylaxis by fire ant venom (Solenopsis sp) and underwent specific immunotherapy. They were assessed at baseline and one year after the beginning of the maintenance phase for skin test; specific venom IgE and IgG4 antibodies; tryptase. Results: All patients included presented a severe anaphylactic reaction. Although two patients (6.25%) presented a tryptase level higher than 11.4 ug/ml, systemic mastocytosis was ruled out. There was no relationship between the severity of the reaction with gender, tryptase level, atopy, previous reactions, the allergen’s concentration in the skin test or specific IgE level. There was an increase in the specific IgG4/IgE ratio between the two time points. Reactions were local, with only two mild systemic reactions during the build-up phase. Twenty patients had accidental stings during immunotherapy, with 3 presenting only urticaria. Conclusions: This study is unprecedented in evaluating clinical and laboratory data in the fire ant immunotherapy. Our results show that after one year of the maintenance phase, patients did not develop any severe reaction with only a few mild reactions and presented a significant production of specific IgG4.