A soluble form of acetylcholinesterase is released from the substantia nigra in both a spontaneous and drug-induced fashion. The aim of this study was to see whether this phenomenon was also sensitive to a non-pharmacological event. During electrical stimulation of the intact sciatic nerve, there was an increase in the activity of acetylcholinesterase, measured in perfusates of the guinea-pig substantia nigra in vivo. This increase was not due to spontaneous fluctuations in acetylcholinesterase release, plasma contamination, tissue damage or release of acetylcholinesterase from a non-specific site. The possible pathways mediating this phenomenon are discussed.