The susceptibility to oral tolerance in post-neonatal infant mice and the effect of a herbal drug, Hochu-ekki-to (HOT), on the susceptibility were investigated. To induce oral tolerance induction, infant and adult mice at 4 and 8 weeks of age, respectively, were orally administered a single high dose of OVA before an intraperitoneal immunization with OVA adsorbed on aluminum hydroxide. HOT (1000 mg/kg) was administered orally for 7 days before the induction. HOT significantly decreased the serum levels of OVA-specific IgE and IgG1 and the antigen-specific proliferation of spleen cells in infant mice, both of which were greatly enhanced compared to in adult mice. HOT increased the number of both CD4 + T cells and antigen-presenting cells expressing MHC class II as well as costimulatory molecules (CD40, CD80 and/or CD86) in the Peyer's patch (PP) of infant mice, which had fewer cells than adult mice. In the PP, moreover, HOT augmented the IL-12p40 mRNA expression and spontaneous or CD40-stimulated IL-12 production, and increased the number of CD4 + cells expressing CD40 ligand, which is up regulated by IL-12. These results suggest that HOT increases the number and improves the function of PP cells that are fully susceptible to the induction of oral tolerance.