The diagnostic usefulness and reliability, in particular in relation to methodologic problems and limitations, of an immunoperoxidase method are discussed, based upon an initial 3-yr experience with more than 400 cases. It has been found necessary to employ certain control preparations in each study case in order to avoid interpretational errors which can derive from variation in distribution of plasma proteins, in preservation of immunoreactivity with different fixatives, and in nonspecific binding of antiserum. The method is suitable for detection of immunoglobulin components only among lymphoid cells corresponding to late stages in the (B-cell) sequence of transformation. One case has been identified in which the results of the method are inconsistent with additional data, that of large cell neoplasm of apparent epithelial nature with a monotypic immunoglobulin staining pattern. Cytoplasmic lysozyme was present in a variety of different disease processes, including adenocarcinoma and granulocytic, monocytic, and histiocytic proliferations.