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ATP is a neurotransmitter in the central and peripheral nervous systems and is also involved in peripheral inflammation and transmission of the sensation of pain. Recently, the regulated release of ATP from nonneuronal sources has been shown to play a role in the activation of sensory nerve terminals. Within the enteric nervous system, which is present in the wall of the gastrointestinal tract, ATP plays three major roles. ATP acts as an inhibitory transmitter from the enteric motor neurons to the smooth muscle via P2Y receptors. ATP is released as an excitatory neurotransmitter between enteric interneurons and from the interneurons to the motor neurons via P2Y and P2X receptors. Finally, ATP may act as a sensory mediator, from epithelial sources to the intrinsic sensory nerve terminals. Thus, ATP participates in the transduction of sensory stimuli from the gut lumen and in the subsequent initiation and propagation of enteric reflexes.