Allergen specific immunoglobulins (IgE, IgG, IgG1, and IgG4) were evaluated during the course of a 12-month specific immunotherapy (ITS) in 27 allergic subjects: 12 Dermatophagoides pteronyssinus (DP)-, 9 Parietaria officinalis (W19)-, six perennial and timothy rye grass (G5 and G6)-sensitive cases. Further, the modifications of the specific Ig levels were compared with the significant improvement in symptoms and drug consumption observed after 12 months of ITS. IgE levels significantly decreased after 6 and 12 months, while IgG1 significantly increased in the early phases of ITS (3rd month), and IgG4 significantly and progressively increased during the course of ITS. No modification was observed in specific total IgG. Regression analysis test among the various Ig levels revealed a strict correlation only between IgE and IgG4 (high levels of IgE before ITS correlated with high levels of IgG4 after 12 months of ITS). No correlation was observed between total Ig changes and improvement of clinical status or drug consumption.