During surgical exposure of the trigeminal root for the treatment of trigeminal neuralgia, biopsy specimens of the nerve root were taken in 12 consecutive patients. The biopsies were taken from areas as close as possible to the site of vascular compression, when present. The tissue was prepared for electron-microscopic evaluation. Except for 1 case, massive disruption of tissue ultrastructure was observed. The major findings included zones of de- and dysmyelination, juxtaposition of denuded axons, apparent axon loss and degeneration, and collagen deposition. Adjacent areas of normal root structure were present in most specimens. The ultrastructural changes observed in the biopsy samples demonstrate important pathology within the trigeminal root. Dysmyelination and the proximity of denuded axons in close apposition to each other support neurophysiological theories of pain production including ectopic electrogenesis, ephaptic contacts, and crossed after-discharge. The findings in this study demonstrate a pathophysiological basis for the syndrome of trigeminal neuralgia.