Specific immunotherapy (SIT) is the only treatment capable of modifying the natural history of the allergic subjects. Several aspects of the immunopathological response modified by sublingual immunotherapy (SLIT) have been investigated; the first parameter historically studied was the production of allergen-specific antibodies. An increase of allergen-specific IgG4 and a decrease of IgE may appear after SLIT. A shift from Th2-polarized immune response toward Th1-oriented pattern has been reported after SLIT. More recently, a crucial role for a subpopulation of T cells has been evidenced: T regulatory (T-reg.) cells. Allergic patients have a defect of T-reg cells. SLIT should be able to induce a specific T-reg. response. SLIT is an alternative route of administration for SIT. Recent evidence shows that SLIT is also able to induce a T-reg. response as detected by IL-10 production.