The effect of prednisolone on IgE-dependent, antigen-induced biphasic cutaneous reaction in BALB/c mice was investigated. 2. The biphasic cutaneous reaction with peak responses at 1 h and 24 h after antigen stimulation was suppressed by prednisolone administered 2 h before the challenge. 3. Although antigen challenge increased the expression of IL-1 beta and TNF-alpha mRNA in the mouse ear, prednisolone did not affect the increase. 4. Anti-IL-1 beta antibodies inhibited the later phase of biphasic cutaneous reaction, whereas anti-TNF-alpha antibodies inhibited both phases of the reaction. 5. Prednisolone inhibited edematous reactions caused by both IL-1 beta and TNF-alpha. 6. Proinflammatory cytokines, such as IL-1 beta and TNF-alpha, participate in the development of the biphasic cutaneous reaction, especially in its later phase, in mice, and prednisolone inhibits the reaction by suppressing the action of cytokines, at least in part.