West Nile virus (WNV) infection can cause severe, potentially fatal neurologic illnesses including encephalitis and meningitis. Acute WNV infection also has been associated with acute flaccid paralysis (AFP) attributed to a peripheral demyelinating process (Guillain-Barré Syndrome [GBS]), or to an anterior myelitis. However, the exact etiology of AFP has not been assessed thoroughly with electrophysiologic, laboratory, and neuroimaging data. This report describes six cases of WNV-associated AFP in which clinical and electrophysiologic findings suggest a pathologic process involving anterior horn cells and motor axons similar to that seen in acute poliomyelitis. Clinicians should evaluate patients with AFP for evidence of WNV infection and conduct tests to differentiate GBS from other causes of AFP.