The cellular and subcellular localization of cationic leukocyte antigen (CLA) in human peripheral blood and tissue granulocytes was investigated by immunoenzymatic labeling and by immunoelectron microscopy. Human peripheral blood granulocytes from healthy individuals and from subjects with eosinophilia of varying etiology, as well as intravascular and/or perivascular granulocytes in skin biopsies taken from patients with generalized onchocerciasis, a skin disease caused by microfilariae of Onchocerca volvulus, were studied. Controlled indirect immunoenzymatic staining for CLA in cytospin preparations of buffy coat cells and in histological sections of skin biopsies revealed that this protein was exclusively found in the cytoplasm of eosinophil granulocytes. Furthermore, immunogold labeling coupled with electron microscopy showed that CLA was specifically localized within the matrix of both the small non-crystalloid-containing pale granules and the large crystalloid-containing secondary granules of peripheral blood and tissue eosinophils. No specific gold labeling was observed in other organelles of eosinophils, in neutrophils, basophils, lymphocytes or monocytes.