Effects of mesenteric nerve (MN) stimulation on the electrophysiological behavior of myenteric neurons in the guinea pig ileum were investigated with intracellular recording techniques in the myenteric flaps innervated with mesenteric nerves. MN stimulation at 0.11-6 Hz evoked fast excitatory postsynaptic potentials (EPSPs) in 6 myenteric neurons (2 Type 2/AH, 3 NS and 1 Type 1/S cells) and rarely evoked antidromic soma spike potentials in 3 myenteric neurons. Fast EPSPs were abolished by hexamethonium. Slow EPSPs evoked by MN stimulation (Takaki and Nakayama (1988) Brain Res., 442, 351-353) were also obtained in 5 Type 2/AH neurons and were irreversibly abolished by superfusion with capsaicin 10 microM. It is, therefore, likely that fast EPSPs mediated by nicotinic cholinergic receptors are due to stimulation of the vagus nerve and slow EPSPs are mediated by a release of substance P at axosomatic synapses due to antidromic activation of the capsaicin-sensitive sensory nerves.</p