Acute or repeated exposure to certain organophosphorus-containing compounds results in a pneuropathy in humans which is well modeled in the adult hen. A large body of evidence suggests that alterations in a protein found in nerve, known as "neurotoxic esterase (NTE)", may be intimately involved in the delayed neurotoxicity of these compounds. Morphological studies indicate that organophosphate neuropathy is best described as a central-peripheral distal axonopathy. However, few attempts have been made to correlate the distribution of NTE with the known location of organophosphate-induced damage. The studies proposed address this important relation. Experiments have been designed to assess the spatial distribution of NTE in a nerve of a susceptible species which is known to degenerate following organophosphate exposure (hen isciaticus nerve). Additionally, studies will determine whether NTE insusceptible distal portions of nerve fiber tracts is affected to the same degree by a prototype neurotoxic organophophate compound (tri-ortho-cresyl phosphate) as that in more proximal less-susceptible portions of nerve fibers. Data will provide, for the first time, information regarding the activity of NTE in organophosphate susceptible and less-susceptible portions of the same nerve fiber. Further studies will determine the role that fast anterograde axonal transport plays in the restoration of NTE activity to the distal portions of vulnerable nerve fibers. Finally, the effect of tri-ortho-cresyl phosphate on anterograde axonal transport of NTE will be evaluated. Data will help clarify the role that NTE plays in the pathogenesis of organophosphate-induced axonopathy. Data obtained from these preliminary studies will be used for the design of future investigations aimed at elucidating the biochemical mechanism of organophosphate-induced distal axonopathy.