Electrical stimulation of interganglionic fiber tracts of Auerbach's plexus released a chemical substance, which produced a slow EPSP associated with an increase in input resistance in the postsynaptic neuron. 2. This effect of fiber tract stimulation was mimicked by microiontophoretic application of serotonin (5-HT) to the neurons. Both the endogenous transmitter substance and exogenous 5-HT produced membrane depolarization, both increased the input resistance of the neuron, both reduced or abolished hyperpolarizing afterpotentials of the action potentials, and both augmented membrane excitability. 3. During tachyphylaxis to excess 5-HT (1 micron) in the perfusion solution, the response to fiber tract stimulation was also reversibly blocked. 4. Methysergide (30 micron) blocked both the response to fiber tract stimulation and to exogenous 5-HT. 5. Cholinergic agonists and antagonists did not alter the slow EPSP and the response to exogenous 5-HT. 6. The evidence suggests that 5-HT is the neurotransmitter substance that produces the slow EPSP in myenteric neurons.
