Recent investigation into a possible association between exposure to Leptophos and neurological symptoms in insecticide factory workers makes study of the neurological effects of Leptophos in the experimental situation particularly important. The present study utilizes a single oral dose of 200 mg/kg of Leptophos in 20 chickens which are sacrificed in pairs to define the temporal sequence of changes in the sciatic nerve, its major branches, and the spinal cord and to correlate these findings with the clinical symptoms of the animals. At this dose Leptophos produces degeneration of the spinal cord in a pattern similar to that seen with tri-o-cresyl phosphate (TOCP). The ataxia seen in these birds is probably due to the posterior and lateral column involvement. At this dose onset of paralysis correlates roughly with both the degeneration of the anterior descending tract of the spinal cord and degeneration of the peripheral nerve. The minimal degree of nerve involvement suggests that the cord lesion is more significant at this dose in the hen. Using TOCP, spinal cord lesions predominate in the hen while the peripheral nervous system appears more sensitive in the human and non-human primate. Assuming that Leptophos resembles TOCP in this regard, peripheral nerve damage would be the expected earliest change, especially in the low-dose situation in the human.