Allergic rhinitis (AR) is characterized by Th2 polarized immune response. Allergen-specific subcutaneous immunotherapy may restore a physiologic Th1 profile. However, there are few studies investigating the immunological effects of sublingual immunotherapy (SLIT). The aim of this study is to investigate whether a pre-seasonal SLIT course could affect IFN-gamma production. Forty-four AR patients with pollen allergy assumed pre-seasonal SLIT for 3 months. IFN-gamma-specific producing cells were assessed by cytokine ELISPOT before and 3 months after the beginning of SLIT. Visual analogue scale (VAS) for symptoms and medication score was also evaluated. The frequency of IFN-gamma-specific producing cells significantly increased after SLIT (p<0.01), and this increase was significantly associated with improvement of both symptoms (p<0.001) and medication use (p<0.01). In conclusion, these results may be considered clinically relevant as SLIT treatment may induce a quick IFN- gamma response that is related to clinical improvement.