The localization of adenosine deaminase (ADA 1) in human tissues was investigated by an immunohistochemical method. Tissues were taken from cadavers, fixed with 4% paraformaldehyde-PBS, and embedded in paraffin, and then examined following immunoperoxidase staining using a rabbit polyclonal antibody against keyhole limpet hemocyanin (KLH)-peptide conjugate (Ser-Phe-Leu-Pro-Glu-Asp-Glu-Lys-Arg-Glu-Leu-Leu) constructed from a human adenosine deaminase cDNA sequence. Immunohistochemical analysis demonstrated that ADA 1 was distributed in various human tissues, with intense reactivity observed in surface epithelia of the esophagus, stomach, small intestine, renal tubules, glandular cells of the small intestine, endothelial lining cells of the liver, and alveoli of the lung. Moderate reactivity was observed in the glomerulus cells of the kidney, epithelia and glandular cells of the large intestine, and hepatic parenchymal cells. This ubiquitous but cell-specific localization suggests that ADA 1 plays an important role in selected cells through the degradation of adenosine, a pharmacological active nucleoside.