✓ In 12 cats and two Macaca mulatta monkeys, areas of chronic focal injury were induced in the trigeminal root by implantation of a chromic suture in the nerve near its entry into the brain stem. Experimental lesions were examined histologically and electrophysiologically at 1 week, 3 weeks, and 6 weeks after surgery. At 3 weeks following implantation, lesioned nerves showed areas of focal inflammation surrounding implanted sutures with prominent demyelination of adjacent axons. A total of 497 trigeminal units were studied, 304 of which had associated demyelination of the root. In these 304 cells, two types of abnormal impulse generation from areas of focal demyelination were recorded. Reflected orthodromic action potentials and prolonged high-frequency after-discharges following short priming trains of orthodromic stimuli were observed in 23% and 4% of cells, respectively. Ectopic spike initiation from areas of focal demyelination was not dependent upon anatomical continuity of the nerve with the brain stem, was augmented by hyperventilation, and could be eliminated by the intravenous administration of diphenylhydantoin sodium. The relevance of these findings to the pathophysiological mechanisms of pain syndromes involving peripheral nerves in general and the trigeminal system in particular is discussed.