We evaluated the immunohistochemical localization of xanthine oxidase in various human tissues. Xanthine oxidase was purified from cadaver liver. Polyclonal antibody against xanthine oxidase was raised in a rabbit. Immunoblot analysis showed that the raised antibody reacted specifically with one band whose position corresponded with that of the purified enzyme. Immunostaining of paraffin-embedded tissue sections showed intense reactivity in the following tissues: surface epithelium of tongue, esophagus, and trachea, sweat glands, and mammary glands. Weak, but positive, reactivity was observed in other tissues, such as glandular cells of the small and large intestine and renal tubules, skeletal muscle, gastric epithelial cells, alveoli of the lung, spleen, and liver cytoplasm. Xanthine oxidase staining was observed in infiltrating lymphocytes (probably T-lymphocytes but not in B-lymphocytes) in inflammatory lesions of the small and large intestine. Its ubiquitous localization suggests that xanthine oxidase is involved in cell proliferation/differentiation, the defense mechanisms, and in the pathogenesis of reperfusion tissue injury.