Perilla frutescens leaf extract (PFE) is known as a natural medicine with anti-allergic activities, although its mechanism of action remains unclear. In this study, we examined the effect of PFE on antigen-specific antibody and on cytokine production. Mice were immunized three times (weekly) with sugi basic protein (SBP), a major allergen of Japanese cedar pollen, in alum adjuvant. PFE was injected intraperitoneally into mice on day 2 before and on the day of each immunization with SBP in alum adjuvant. Serum anti-SBP IgE and IgG 1 antibody levels were significantly suppressed in mice injected with PFE. Furthermore, the production of interleukin (IL)-4, IL-5 and IL-10 by SBP-stimulated splenocyses also decreased in PFE-injected mice in a dose-dependent manner. However, PFE had no effect on either the serum anti-SBP IgG 2 a antibody levels or on interferon (INF)-gamma production by splenocytes. When splenocytes were stimulated with concanavalin A, there was no difference in cytokine production between mice injected with PFE and control mice injected with vehicle. SBP-specific T cell line established in the presence of PFE from the lymph node cells of mice immunized with SBP showed reduced IL-4, IL-5 and IL-10 production compared with that established in the absence of PFE. In contrast, comparable levels of IFN-gamma production were observed between these two T cell lines. These data suggest that PFE down-regulates Th 2-type cytokine production and prevents the Th 1/Th 2 balance from polarizing toward Th 2-type immune responses.