Demyelinating lesions in the trigeminal root were produced by chronic implantation of chromic suture in 12 cats. Two types of abnormal repetitive action potential generation were recorded from demyelinated fibers: reflected spikes and afterdischarge. Both types of abnormal impulse generation were increased by hypocalcemia induced by disodium edetate infusion, hypocapnia produced by hyperventilation, and, to a lesser extent, alkalosis secondary to sodium bicarbonate administration. This hyperexcitability of fibers could be inhibited by hypoventilation with elevation of PaCO2 or by calcium chloride administration. These results may help explain the pathophysiological basis of paroxysmal symptoms in multiple sclerosis and other disorders in which demyelination is a prominent feature.