The pathophysiology of hepatic neuropathy is poorly understood, but membrane depolarization due to a toxic inhibition of oxidative metabolism has been proposed. We investigated the relationship between nerve excitability properties, nerve dysfunction, and liver function in 11 pretransplant patients, the majority of whom were oligo- or asymptomatic for peripheral neuropathy. Abnormalities were detected on clinical examination (6), large-fiber nerve conduction (4), and thermal quantitative sensory testing (10). Small-fiber involvement was characterized by elevation of warm more than cold detection thresholds. Autonomic dysfunction was less frequent (4). Nerve excitability parameters in both upper and lower limbs provided evidence of membrane depolarization compared with controls, even in those patients without a history of alcohol abuse. No clear correlation was found between neurophysiological indices and scores of hepatic reserve or various blood parameters including ammonia level. Although chronic membrane depolarization may be involved, the degree of depolarization in large fibers was small, and its role in the pathophysiology of neuropathy uncertain.