Effect of 50% ethanolic extract of unripe fruits of Citrus unshiu (CU-ext) on type IV allergic reaction was examined by inhibitory activity of ear swelling of picryl chloride-induced contact dermatitis (PC-CD) in mice. Oral administration of CU-ext and subcutaneous administration of prednisolone showed inhibition of ear swelling during both induction and effector phases of PC-CD. The inhibitory activities of combinations of CU-ext (p.o.) and prednisolone (s.c.) during induction phase of PC-CD were more potent than those of CU-ext alone and prednisolone alone. Successive oral administration of hesperidin, a major flavanone glycoside of CU-ext, inhibited ear swelling during induction phase of PC-CD. The inhibitory activities of combinations of hesperidin (p.o.) and prednisolone (s.c.) were more potent than those of hesperidin alone and prednisolone alone. These results indicated that the combinations of prednisolone and CU-ext or hesperidin exerted a synergistic effect.