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Black cohosh (Cimicifuga racemosa) has been used as therapeutics for pain and inflammation in Korean folk medicine. The potential effects of black cohosh extract (BCE) on mast cell-dependent allergy reaction, however, have not been well elucidated yet. In the present study, we investigated the effect of BCE on the allergy reaction using mast cell-dependent in vivo and in vitro models. BCE showed no potential of skin sensitization in local lymph node assay (LLNA). The oral administration of BCE significantly inhibited the anti-IgE-induced passive cutaneous anaphylaxis (PCA) reaction. BCE also showed inhibitory potential on the compound 48/80-induced histamine release from rat peritoneal mast cells. In addition, BCE inhibited the IL-4, IL-5 and TNF-alpha mRNA induction by PMA and A23187 in human leukemia mast cells, HMC-1. These results demonstrated that BCE has an anti-allergic potential and it may be due to the inhibition of histamine release and cytokine gene expression in the mast cells.