Interstitial cells of Cajal (ICC) are a fundamental component of the pacemaker apparatus of the gastrointestinal (GI) tract. ICC generate pacemaker currents that are the basis for slow wave activity in GI muscles. ICC form a network of cells connected by gap junctions that run around and along the phasic regions of the GI tract. ICC possess specialized conductances that allow them to generate pacemaker activity and serve as the pathway for active propagation of slow waves. Pacemaker currents are attributed to a Ca(2+)-inhibited, voltage-independent, non-selective cation conductance that has similar properties to the conductance elicited by expression of transient receptor potential-C4. Propagation occurs through a voltage-dependent mechanism, and data suggest that the factor coupling pacemaker units in ICC is Ca(2+) entry. ICC express a dihydropyridine-resistant, voltage-dependent Ca(2+) conductance that is important in slow wave propagation. Work is underway to determine the molecular identities of these conductances.