The clinical records of nine patients, followed at the University of Chicago, with mycosis fungoides (MF) and neurologic deficits due to direct CNS involvement were reviewed. Lymph node and visceral involvement was present in all patients. Clinical findings included cranial nerve deficits in four patients, altered mental status in eight, gait disturbances in three, and leg weakness in one. Helpful diagnostic studies included lumbar puncture with CSF cytology, computerized tomography (CT) brain scans, brain biopsy, and myelogram. Two patients, who were treated with radiation therapy (RT), survived 14 and 40 weeks, respectively. Survival of less than 4 weeks limited treatment in the other patients. Autopsies were performed on six patients and revealed meningeal infiltration and perivascular infiltration of the brain. In addition, the cerebral parenchyma was infiltrated in one patient and a lymphomatous tumor was found in the brainstem of another. We conclude that the varied clinical and pathologic features of CNS involvement with mycosis fungoides resemble those seen in leukemias and other lymphoproliferative disorders. Better awareness of the clinical features may permit earlier diagnosis and initiation of therapy.