Mast cells synthesize and secrete chemical mediators which play an central role in anaphylactic reactions. Compound 48/80 is a condensation product of formaldehyde with paramethoxyphenylethylamine that reliably induces the release of chemical mediators in the mast cell granules. Aggregation of the high-affinity Fc receptor also stimulates the mast cells. The objective of the current study was to determine the effect of Sosiho-Tang (SS-Tang) on mast cell-mediated anaphylactic reaction. SS-Tang completely inhibited systemic anaphylaxis induced by compound 48/80 in mice. SS-Tang inhibited local anaphylaxis induced by anti-dinitrophenyl (DNP) IgE. In addition SS-Tang concentration-dependently inhibited histamine release in mast cells induced by compound 48/80 or anti-DNP IgE. These results indicate that SS-Tang may contain compounds with actions that inhibit mast cell degranulation.