The effects of 17β-estradiol (E2) on mouse contact hypersensitivity (CHS) elicited at the ears by 4-ethoxymethylene-2-phenyl-2-oxazolin-5-one (OXA) were examined. Male and female BALB/c mice were sham-treated or gonadectomized, and then subcutaneously injected with E2 twice a week for 4 weeks. The mice were sensitized by OXA application to their back and CHS was elicited at the ears. E2 enhanced the ear swelling of all groups at 6 h after the elicitation. E2 had no effect on the mitogenesis of splenic lymphocytes or nitric oxide synthesis by peritoneal macrophages. E2 increased the number of thymic cells in female mice, but not male mice, and had no effect on the splenic cells of either female or male mice. Evaluation of the cytokine expressions in the inflamed skin revealed that E2 enhanced the expression of interferon-γ, but had no effect on the expression of interleukin-4. These results suggest that E2 affects the thymus and enhances the production of interferon-γ in skin to augment the skin swelling in CHS elicited by OXA.