With the aim of finding characteristics pointing to the primary site, computed tomography examination from 9 patients with primary brain malignant lymphoma (non-Hodgkin's lymphoma originating in the central nervous system, NHL-CNS) (5 single, 4 multiple lesions) were analyzed. The tumors were usually situated in the basal ganglia, corpus callosum, or cerebellum and were always in contact with either the ependyma of the ventricles or the subarachnoid space. Tumors with widespread infiltration of white matter surrounding the ventricles were characteristic of NHL-CNS. Microscopic examination of 3 autopsy cases revealed infiltration of the subependymal layer of the lateral ventricles and the third and fourth ventricles by lymphoma cells. The entire extent of the choroid plexus was invaded by tumor cells. There were multiple foci of similar cells invading the periventricular white matter. The subarachnoid space was filled with lymphoma cells. In many areas the Virchow-Robin spaces and pial-glial membranes were disrupted, and invasion of the underlying gray matter by tumor cells was seen. The ultrastructure of the blood vessels of NHL-CNS was compared with those in glial, nonglial, and metastatic brain tumors. The essential feature in NHL-CNS was fenestrated vessels. They resembled the blood vessels found in nonglial and metastatic brain tumors, but were distinctly different from those seen in glial tumors with nonfenestrated vessels. Although the following scheme in proposed with reservations, it could account for the sites of origin of NHL-CNS: lymphocytes located in the choroid plexus stroma or the subarachnoid space are activated, caused to proliferate, and finally become neoplastic. Then these cells migrate through the underlying parenchyma along the Virchow-Robin spaces and multiply until they present themselves as primary brain tumors.