The effects of agonists and antagonists of nicotinic, muscarinic (M1 and M2), and adrenergic receptors on migrating spike complexes (MSC) in ileum of fasting cats are reported. Hexamethonium decreased MSC frequency and blocked propagation. Atropine at low concentrations increased MSC frequency and increased velocity of propagation; atropine at high concentration blocked propagation. Pirenzepine (Pz; M1 antagonist) increased MSC frequency and propagation velocity. McNeil A-343 (M1 agonist), by a Pz-sensitive phentolamine-insensitive mechanism, and 4-diethylamine-methylpiperidine (4-DAMP; M2 antagonist) blocked propagation of an ongoing MSC but had no significant effect on frequency or velocity. Bethanechol (M2-receptor agonist) increased phasic spiking by a 4-DAMP-sensitive mechanism and blocked MSC propagation by a Pz-sensitive mechanism. Phenylephrine (alpha 1-adrenoceptor agonist) or oxymetazoline (alpha 2-adrenoceptor agonist) blocked MSC propagation but had no effect on MSC frequency or velocity. Phentolamine (nonselective alpha 1-adrenoceptor antagonist), prazosin (alpha 1-adrenoceptor antagonist), or yohimbine (alpha 2-adrenoceptor antagonist) alone had no effect on MSC activity. The conclusion is that the enteric nervous system controls and regulates the MSC by the following proposed mechanisms. 1) M1-muscarinic receptors, located either on postganglionic inhibitory neurons or presynaptically at a nicotinic synapse and/or neuromuscular junction, are involved in the tonic inhibitory control of MSC initiation and propagation. 2) Nicotinic and M2 muscarinic receptors, located on excitatory postganglionic motoneurons and smooth muscle cells, respectively, are important in the initiation and/or propagation of MSC. 3) alpha 1-Adrenoceptors on the smooth muscle cells and alpha 2-adrenoceptors located presynaptically at the nicotinic ganglionic synapses are not tonically active but inhibit MSC activity (4). Smooth muscle beta-adrenoceptors do not play a significant role in neural control of MSC activity.