The effects of tacrolimus ointment on immediate, late and delayed-type cutaneous allergic reactions and normal skin thickness were investigated in mice and compared with those of steroid ointments. Tacrolimus ointment had no effect on ear edema in the immediate phase of the biphasic reaction and did not inhibit passive cutaneous anaphylaxis, but in the late phase of the biphasic reaction, it inhibited the ear edema. It also showed a clear inhibitory effect on the delayed-type reaction. These evidence suggest that the clinical effect of tacrolimus ointment against atopic dermatitis (AD) may be mainly due to its inhibitory action on late and delayed-type reactions. The steroid ointments inhibited all the reactions mentioned above, and the effects were more potent than those of tacrolimus. Moreover, they also decreased the normal ear thickness, suggesting that the inhibitory effect of the steroid ointments was partially due to skin atrophic action. The same ointments applied to the ears during the induction phase showed an enhancement of delayed-type reaction at the effector phase. Tacrolimus ointment did not show such a rebound effect or skin atrophy. Thus, tacrolimus ointment was expected to be more useful than the steroids for the treatment of AD.