Total external ophthalmoplegia was observed in five patients consequent to the oral or intravenous administration of phenytoin. Coincident with the ophthalmoplegia, the state of consciousness varied from drowsiness to coma and the blood levels of phenytoin ranged from 36 to 55 mug per milliliter. Initially, the eyes were fixed in midposition, and oculocephalic and oculovestibular stimulation failed to evoke either horizontal or vertical eye movements. The return of vestibulo-ocular responsiveness lagged behind the return of consciousness and other reflex activity. The mechanism underlying this ophthalmoplegia may be related to the ability of phenytoin to potentiate inhibitory synapses in the vestibulo-oculomotor pathway which utilize gamma aminobutyric acid, and to increase the discharge rate of Purkinge cells which exert an inhibitory influence on the same structures.