Neurotoxic chemicals commonly produce retrograde degeneration of the axons of long and large nerve fibers in the central and peripheral nervous system. This produces a clinical picture of polyneuropathy in man and animals in which sensory and motor disturbances develop in the feet and hands then progress with time to the legs and arms. Distal axonopathy, as the underlying pathologic process is termed, is one of four principal types of neurotoxic diseases, the others including degeneration of neurons (neuronopathy), myelin sheaths (myelinopathy) and damage to the neurovasculature (neurovasculopathy). In the experimental animal, these four types of neurotoxic diseases can be distinguished by examining selected areas of brain and nerve tissues prepared by contemporary methods of tissue fixation. These procedures may form the basis of a new and sensitive assay for neurotoxicity.