Allergic rhinitis (AR) is characterized by Th2 polarized immune response, such as increased IL-4 and reduced IFN-y production. Sublingual allergen-specific immunotherapy (SLIT) induces several immunological changes, most of which are still little known. The aim of this study is firstly to investigate the changes of allergen-specific IgE, IgG, IgG4, and IgA serum levels after SLIT. Secondly, this study aims at relating immunoglobulin (Ig) values with some Th l-, Th2-, and Treg-dependent cytokines. Twenty-three patients with pollen-induced AR were enrolled, and they assumed two pre-seasonal SLIT courses for 2 years. Serum allergen-specific IgE, IgG, IgG4 and IgA levels were determined by ELISA method at baseline and after each SLIT course. Serum IL-4, IFN-y, IL-IO, and TGF-[3 levels were also assessed. Allergen-specific IgE, IgG, IgG4, and IgA serum levels significantly increased after SLIT. Serum TGF-[3 significantly increased after SLIT. There was a significant correlation between IgA and TGF-[3, both after the first and the second SLIT course. In conclusion, the present study provides the first evidence that pollen SLIT significantly affects Ig production, mainly concerning IgA; and IgA increase is related with TGF-[3 production. Moreover, this is the first study that measured Ig classes by using a quantitative method.AR management includes patient education, allergen avoidance, drug therapy, and, when appropriate, allergen-specific immunotherapy (SIT) (1). SIT is the practice of administering gradually increasing doses of the causal allergen in order to reduce allergic symptoms resulting from exposure and the need for medications. These effects depend on achieving clinical tolerance of the causal allergen. For these reasons SIT is also called "anti-allergic vaccine". There is evidence that SIT is effective in patients with allergic rhinitis and mild forms of asthma, as stated in a WHO position paper (2).SIT is classically based on the subcutaneous administration of allergen extracts (SCIT), but this route of administration has shown a risk of serious adverse reactions; the sublingual (SLIT) route of immunotherapy was therefore investigated and developed as an alternative. The rationale of SLIT is that oral administration of high-dose allergen may reduce and prevent IgE responses. Methodologically, the extract is kept under the tongue for a few minutes and then swallowed: the so-called sublingual-