Immunohistochemical detection of intracellular myeloperoxidase, a major constituent of primary granules of neutrophilic myeloid cells, was determined in paraffin sections of 161 specimens using a rabbit polyclonal antibody to human myeloperoxidase and an indirect immunoperoxidase technique. In normal tissues and in a variety of myeloproliferative disorders, myeloid cells of both neutrophilic and eosinophilic types, at all stages of maturation, exhibited strong cytoplasmic reactivity for myeloperoxidase. Myeloperoxidase was readily detected in myeloblasts and immature myeloid cells of acute myelogenous leukemia, progranulocytic leukemia, monomyelocytic leukemia, erythroleukemia, myeloblastomas, and other hematopoietic disorders. Erythroid precursors, megakaryocytes. other hematopoietic disorders. Erythroid precursors, megakaryocytes, lymphoid cells, mast cells, and plasma cells were nonreactive. Cells of monocytic derivation revealed variable reactivity and were typically weakly positive or nonreactive. In a few specimens, rare histiocytes were reactive, some possibly due to phagocytosed material. Cells comprising the infiltrate of a spectrum of lymphoid malignancies, eq, lymphoblastic lymphoma or leukemia, chronic lymphocytic leukemia, hairy cell leukemia, non-Hodgkin's lymphomas of T-or B-cell type, and Hodgkin's disease, were nonreactive, as were the non-neoplastic tissues present in these specimens, except for occasional cells of myeloid derivation. Myeloperoxidase was not observed in the neoplastic cells of a wide variety of epithelial tumors and sarcomas, or in the contiguous non-neoplastic tissues. Immunoreactivity for myeloperoxidase was well preserved following fixation in a variety of fixatives, including Zenker's-acetic acid solution (employed for processing bone marrow biopsies), B5 solution, and formalin. Immunohistochemical detection of myeloperoxidase represents a sensitive and highly specific technique for identification of mature and immature myeloid cells in paraffin-embedded tissue.