Rats were dosed once daily with pyridostigmine 2 mgkg over a 20 day period. Groups of animals were assessed at intervals for changes in enzyme activity and nerve and muscle electrophysiologic activity. There was a marked inhibition of both acetylcholinesterase AChe and butyrylcholinesterase BuChE activity within 15 minutes of dosing. The activity recovered by 24 hours. There were no changes in nerve, spinal cord, or brain enzyme activity AChE, BuChE, neurotoxic esterase, carboxylesterase. Likewise, there were no changes in the compound action potential of either the sural or sciatic nerve and no changes in the sciatic nerve responsiveness to extracellular potassium. The triceps surae muscles responded normally to tetanic stimulation during the course of the experiment. Initial work has begun, using ALZET pumps to deliver constant infusions of either pyridostigmine or physostigmine.