Primary gastrointestinal lymphomas (PGLs) are the most frequent extranodal non-Hodgkin's lymphomas and involve stomach more commonly than small bowel in Western countries. PGLs need to be differentiated from a variety of tumor-like hyperplastic lymphoid lesions; this may be facilitated by immunotyping of lymphoid cells. In PGLs, large-cell types predominate. Our study of 76 PGLs utilizing the ABC immunoperoxidase technique has led us to conclude that the majority are of B cell origin and that, while true histiocytic PGLs do indeed exist, their incidence is not greater than in nodal lymphomas. An important observation was that 26% of the cases showed an intense admixture of muramidase-positive reactive histiocytes, a feature that could result in an erroneous impression of a histiocytic derivation of the neoplasm. The prognostic significance of immunologic subtypes is currently not known. However, survival in PGL is determined by the clinical stage of the disease and to a lesser extent by the histologic type. Current optimal therapy includes resection of tumor-bearing bowel followed by radiotherapy and/or chemotherapy.