We report the clinical and immunohistochemical features of six cases of intravascular lymphomatosis. All patients presented with symptoms referable to central nervous system (CNS) involvement. In two patients, the diagnosis was made on brain biopsy specimens. In the remaining four cases, diagnosis was made at autopsy. Three of the four autopsied patients had focal extravascular lymphoma, diffuse large cell type. In all five cases tested, immunohistochemical stains on paraffin-embedded sections confirmed the lymphoid nature of the malignant cells. Stains on frozen sections in one case, and on paraffin-embedded tissue in the other four cases, demonstrated B-lymphocyte lineage. In the remaining case, electron microscopy confirmed the lymphoid nature of the tumor cells. All three cases tested expressed the Hermes 3-defined homing receptor antigen and lacked peanut agglutinin receptors. Our results are consistent with other reports confirming the lymphoid nature of so-called malignant angioendotheliomatosis. Our limited analysis of surface receptor molecules suggests that the expression of the homing receptor for high endothelial venules is not in itself responsible for the unusual intravascular location of these cells.