Ion channels play key roles in determining smooth muscle tone by setting the membrane potential and allowing Ca2+ influx. Perhaps not surprisingly, therefore, they also provide targets for neurotransmitters and other messengers that act on smooth muscle. Application of patch-clamp and molecular biology techniques and the use of selective pharmacology has started to provide a wealth of information on the ion channel systems of smooth muscle cells, revealing complexity and functional significance. Reviewed are the actions of messengers (e.g., noradrenaline, acetylcholine, endothelin, angiotensin II, neuropeptide Y, 5-hydroxytryptamine, histamine, adenosine, calcitonin gene-related peptide, substance P, prostacyclin, nitric oxide and oxygen) on specific types of ion channel in smooth muscle, the L-type calcium channel, and the large conductance Ca(2+)-activated, ATP-sensitive, delayed rectifier and apamin-sensitive K+ channels.