Epstein-Barr virus infection can affect both the central and peripheral nervous system. In some patients this occurs concurrently. Two patients are presented with encephalopathy and acute quadriparesis with diminished reflexes. Positive serology for Epstein-Barr virus was found in both patients. Both patients had a cerebrospinal fluid pleocytosis in the setting of progressive weakness. Electrophysiologic studies early in the course of their illness demonstrated abnormal F-wave latencies with normal distal conduction. Electromyographic studies demonstrated prominent spontaneous activity in affected limbs. As both the encephalopathy and weakness improved, the electrophysiologic abnormalities improved. This presentation is characteristic of acute Epstein-Barr virus infection. Pathologic studies in other patients have documented both anterior horn cell degeneration and edema as well as cellular infiltration of nerve roots which are responsible for the paralysis with diminished reflexes and electrophysiologic findings. The prognosis for these patients is generally good.