Neuropharmacological studies of Schistosoma mansoni were conducted in vitro using visual observations of motor activity and measurements of worm length and extracellular electrical activity. The instrumentation and methodology described quantitatively measure extracellular electrical potentials associated with motor activity, and provide a highly sensitive, objective technique for studying effects of antischistosomal compounds and for evaluating schistosomes as a model for neuropharmacological investigation. The visual motor and electrical responses of schistosomes to various pharmacological agents support earlier claims for the presence of an excitatory tryptaminergic system and an inhibitory cholinergic system. The stimulation of motor activity by 5-hydroxytryptamine was blocked by the antagonists metergoline and cyproheptadine in a dose-dependent manner. The hypermotility induced by cholinergic blockade (atropine or mecamylamine) or 5-hydroxytryptamine release (p-chlorophenylethylamine) was abolished by these antagonists. The cholinomimetic agents, acetylcholine, carbachol and arecoline, and the cholinesterase inhibitors neostigmine and metrifonate, caused a flaccid paralysis of schistosomes. Carbachol-induced paralysis was reversed by both the nicotinic cholinergic blocker, mecamylamine, and the muscarinic cholinergic blocker, atropine. This reversal occurred in a dose-dependent manner. It is suggested that the cholinoceptive site in S. mansoni has unique pharmacological properties, distinctly different from those in mammals. Dopamine, apomorphine, epinephrine and norepinephrine had little effect on schistosome motility, but produced marked increases in worm length. The dopaminergic antagonist, haloperidol, completely blocked the dopamine response. A broad range of putative amino acid neurotransmitters failed to alter schistosome motor activity. The simple nervous system of the schistosome appears to have many unique pharmacological features which may make it a useful model for the study of drugs for human use, as well as providing an effective point for chemotherapeutic attack.