To compare electrical field stimulation (EFS) with nicotine in the stimulation of excitatory and inhibitory enteric motor neurons (EMN) in the human esophagus, circular lower esophageal sphincter (LES) and circular and longitudinal esophageal body (EB) strips from 20 humans were studied in organ baths. Responses to EFS or nicotine 100µM were compared in basal conditions, following N^G-nitro-L-arginine (LNNA) 100µM, and following L-NNA and apamin 1µM. Results: LES strips developed myogenic tone enhanced by TTX 5µM or L-NNA. EFS-LES relaxation was abolished by TTX, unaffected by hexamethonium 100µM, and enhanced by atropine 3µM. Nicotine-LES relaxation was higher than EFS-relaxation, reduced by TTX or atropine, and blocked by hexamethonium. Following L-NNA, EFS elicited a strong cholinergic contraction in circular LES and EB, and nicotine elicited a small relaxation in LES and no contractile effect in EB. Following L-NNA and apamin, EFS elicited a strong cholinergic contraction in LES and EB, and nicotine a weak contraction amounting to 6.64±3.19% and 9.20±5.51% of that induced by EFS. EFS elicited a contraction in longitudinal strips; following L-NNA and apamin, nicotine did not induce any response. Conclusions: Inhibitory EMN tonically inhibit myogenic LES tone, and are efficiently stimulated both by EFS and nicotinic acetylcholine receptors (nAChRs) located in somatodendritic regions and nerve terminals, releasing nitric oxide (NO) and an apamin-sensitive neurotransmitter. In contrast, although esophageal excitatory EMN are efficiently stimulated by EFS, their stimulation through nAChRs is difficult and causes weak responses, suggesting the participation of non-nicotinic mechanisms in neurotransmission to excitatory EMN in human esophagus.