The immunoarchitecture of five cutaneous pseudolymphomas was studied by staining serial sections for T-and B-cell and dendritic reticulum cell (DRC) antigens with monoclonal antibodies, and compared with that of reactive lymph nodes and cutaneous lymphoma. In four cases compartmentalization of B and T cells was observed, analogous to findings in reactive lymph nodes. In two of these cases the immunoarchitectural features were strikingly similar to those of reactive lymph nodes. Both had distinct follicles with germinal centers, and in one distinct mantle zone formation was seen. B cells in the follicles were polyclonal, with κ chain predominance. The germinal centers showed the expected intercellular and/or dendritic pattern of immunoglobulin heavy chain, B2, and DRC-antigen expression. T cells admixed in the germinal centers were overwhelmingly of the T-helper type. The B-cell compartments in the other two cases showed some subtle immunologic evidence of aberrance, but the weight of evidence suggested reactive/aberrant rather than malignant processes. The T-cell compartments in all four cases showed a predominance of T-helper and a minority of T-suppressor/cytotoxic cells. All contrasted with the lymphomas, which showed B-cell monoclonality, markedly deranged T-subset proportions, or novel T-cell phenotypes. Although the main focus of this study was cases involving substantial populations of both B and T cells, preliminary observations were made in one case in which a predominance of T cells and prominent epidermotropism simulated mycosis fungoides. Quantitative ultrastructural analysis in this case suggested a reactive T-cell process. Leu-6-positive Langerhans cells were increased in the epidermis and dermis in all five cases, and in the dermis they were found almost exclusively in T-cell compartments. It is proposed that this distribution is the anatomic correlate to the known functional role of Langerhans cells in antigen processing/presentation and T-cell activation. In the cutaneous "lymph node equivalent", Langerhans cells are analogous to interdigitating reticulum cells of reactive lymph nodes in distribution and, probably, in function. The DRC found in the germinal centers in two cases were probably antigenically identical and functionally analogous to those in germinal centers of reactive lymph nodes. Immunologic phenotyping of serial cutaneous sections may aid in distinguishing reactive from neoplastic lymphoid lesions. Immunoarchitectural analysis promises to be a powerful tool for the study of lymphoproliferative disease.