We evaluated serum glial fibrillary acidic protein (GFAP) levels by enzyme-linked immunosorbent assay (ELISA) in controls (n = 30) and in patients with chronic sensory-motor axonal neuropathy (CSMAN) (n = 30), chronic inflammatory demyelinating polyneuropathy (CIDP) (n = 30), multifocal motor neuropathy (MMN) (n = 30), and primary muscular spinal atrophy (PMSA) (n = 15). GFAP levels, expressed as optical density, were increased in CSMAN (median = 1.05) compared to controls (median = 0.41; P < 0.05) and CIDP (median = 0.53, P < 0.05). They were also increased in PMSA (median = 0.99) compared to controls (P < 0.05) and MMN (median = 0.66; P < 0.05). To differentiate CSMAN from CIDP and PMSA from MMN, we applied a cutoff of GFAP levels at 0.66, and we obtained good sensitivity and specificity. In neuropathies, serum GFAP correlated with summated sensory nerve action potential amplitudes (r = -0.57; P = 0.0006) and disease severity (r = 0.37; P = 0.0011). Thus, we propose serum GFAP as a marker of axonal damage and severity in chronic neuropathies.