Although immunotherapy is recognized as a highly effective form of treatment for allergic rhinitis, especially pollen-induced seasonal allergic rhinitis, the mechanisms have not been fully established. In the present study, we investigated whether immunotherapy could affect the seasonal increase in interleukin-5 (IL-5) in the serum of patients with seasonal allergic rhinitis and whether the effect on IL-5 in serum is related to the clinical efficacy of immunotherapy. Venous blood was collected twice from each patient with seasonal allergic rhinitis due to Japanese cedar pollens, before and during the cedar pollen season in 1997, to determine the cedar pollen-specific IgE and IL-5 in serum. Both specific IgE and IL-5 in serum were significantly increased during the pollen season, not only in the poor responders to antihistamines but also in the good responders. Neither the rate of seasonal increase in specific IgE nor the rate of seasonal increase in IL-5 differed significantly between the good responders and the poor responders to antihistamines. Both specific IgE and IL-5 were significantly increased during the pollen season in the poor responders to immunotherapy, whereas neither specific IgE nor IL-5 was increased during the pollen season in the good responders to immunotherapy. The rate of seasonal increase in specific IgE as well as IL-5 was significantly smaller in the good responders than in the poor responders to immunotherapy. The rates of seasonal increase in specific IgE and in IL-5 were inversely correlated with the length of time on immunotherapy. However, the rate of seasonal increase in specific IgE was not significantly correlated with the rate of seasonal increase in IL-5. In conclusion, the suppression of the seasonal increase in IL-5 in serum is a working mechanism of immunotherapy related to the clinical efficacy of the treatment.