Based on post-mortem neuropathological evaluation the authors analyzed the incidence and distribution of the lymphomatous infiltrates within the leptomeninges and spinal roots in 21 patients with high grade non-Hodgkin's lymphomas (HGNHL) treated with intrathecal methotrexate (ITMTX) prophylaxis. The investigations revealed that lymphomatous infiltrates were most frequent within cerebellar leptomeninges and around spinal roots. In spinal leptomeninges and roots the infiltrates occurred significantly rare after more than 3 ITMTX injections, but further ITMTX applications did not diminish infiltrates incidence in the mentioned regions. In the remaining regions infiltrates incidence was similar, irrespective of the number of ITMTX injections. From the neuropathological point of view ITMTX prophylaxis isn't able to prevent the development of the infiltrates in the mentioned regions. In an attempt to determine the clinical usefulness of the ITMTX prophylaxis in adult patients with HGNHL and to elaborate optimal prophylactic management, the more detailed clinical and pathological evaluations are required.