The participation of tumor necrosis factor-alpha (TNF-alpha) in a IgE-mediated cutaneous reaction in WBB6F1-W/Wv (W/Wv), mast cell deficient, mice and the effect of prednisolone on this cutaneous reaction were investigated. Mice were passively sensitized by an intravenous injection of monoclonal anti-dinitrophenol (DNP) IgE, and their ears challenged epicutaneously with dinitrofluorobenzene 24 h later. The cutaneous reaction estimated by ear thickness reached a peak 48-72 h after the antigen challenge. A monoclonal anti-tumor necrosis factor (TNF)-alpha antibody inhibited the IgE-mediated cutaneous reaction. An increase of TNF-alpha mRNA was demonstrated 4 h after the application of antigen by the reverse transcriptase-polymerase chain reaction. The injection of recombinant murine TNF-alpha induced a cutaneous reaction which peaked at 24 h in nonsensitized mice. Prednisolone at doses of 3 to 10 mg/kg clearly inhibited the IgE-mediated cutaneous reaction, however, it did not affect the expression of TNF-alpha-mRNA. Prednisolone at doses of 1 to 10 mg/kg clearly inhibited the TNF-alpha-induced cutaneous reaction. These results suggest that TNF-alpha plays a role in the IgE-mediated cutaneous reaction in W/Wv mice and that prednisolone inhibits the cutaneous reaction at least in part by inhibiting the action of TNF-alpha.