Some organophosphorous acid triesters (OP) can cause distal (delayed) neuropathy in mammals and avians. Neural membrane-bound carboxylesterase(s) (neuropathy target esterase(s), NTE) is considered to be a target for the neuropathic OP. We report here two additional processes that may be involved in pathogenesis of the distal neuropathy. First, stability of the high-molecular weight microtubule-associated proteins isolated from chickens with OP-induced distal neuropathy diminished, presumably due to hydrolysis catalyzed by Ca²⁺-activated protease(s). Second, recently we used Ca²⁺-dependent phospholipase A₂(PLA₂) for solubilization of NTE from neural membranes. A selective destruction of neural membranes due to PLA₂-catalyzed hydrolysis of membrane phospholipids was the primary mechanism of NTE solubilization. Lysophospholipids formed from the membrane phospholipids were efficient detergents for solubilization of membrane-bound carboxylesterases, a quality that may have contributed to NTE solubilization. Our working hypothesis considers release of Ca²⁺ as a speculative event that results in activation of both enzymes and triggers destabilization of microtubules and damage to neural membranes in OP-induced distal neuropathy.