A 24 year-old man experienced a left retrobulbar neuritis which improved completely after 2 months of non-steroid antiinflammatory therapy. One month after the end of the treatment he developed a Korsakoff-like amnestic syndrome. Three months later he complained of horizontal diplopia. A CT Scan showed a diffuse enhancement of the periventricular areas, corpus callosum and fornix. Diplopia and CT scan abnormalities disappeared after the administration of tetracosactide. Subsequently a progressive worsening of the neurological condition developed, including a 1 1/2 syndrome of Fisher. In C.S.F. proteins ranged from 35 to 66 mg/dl, gammaglobulins from 4 to 5 per cent, cells from 2.2 to 6.8 per mm3 without abnormal cells. Rounded areas of enhancement were observed on CT scan in pons and right occipital lobe. Usual biological tests, abdominal echography and lymphography were normal. Death occurred 15 months after the onset of symptoms. Neuropathological examination showed: 1) a cerebral lymphoma of probable B origin with distinct masses in right occipital lobe and pontine tegmentum and a more diffuse perivascular infiltration on the left side in the amygdaloid nucleus, fourth temporal gyrus, sublenticular area, hypothalamus and in the right internal capsule; 2) multiple small clear-cut foci of demyelination with myelin-axonal dissociation bilaterally in the optic pathways, periventricular regions, corona radiata, cerebral and cerebellar white matter, sublenticular areas, temporal lobes, splenium of the corpus callosum and fornices with secondary atrophy of the mamillary bodies. Both recent and old plaques were observed. Inflammatory perivascular cuffing, when present, consisted of small nontumoral lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)