Biphasic skin reactions, with peaks at 1 and 24h after epicutaneous challenge with antigen (immediate phase response : IPR and late phase response : LPR, respectively), were induced in ddY, ICR, Balb/c and Balb/c-nu/nu mice passively sensitized with monoclonal IgE antibody 24h before. In WBB6F₁-W/W^v mice, which lack mast cells, only the LPR was observed. The IPR was characterized by a rapid increase in capillary permeability and the LPR by skin thickening with significant infiltration of eosinophils and other inflammatory cells in Balb/c mice. Histamine H₁ receptor antagonists, including diphenhydramine and homochlorcyclizine, and the allergic histamine release inhibitors, tranilast and amlexanox, clearly inhibited the IPR, but not the LPR. Prednisolone and dexamethasone, however, inhibited both. Prednisolone also inhibited the LPR in WBB6F₁-W/W_v mice. These results indicate that IgE antibody-dependent biphasic skin reactions consist of a mast cell-and histamine-dependent IPR and a mast cell-independent LPR.