The structural and functional bases of pacemaking (slow waves) in porcine ileal circular muscle were studied. The myenteric plexus contained two, structurally distinct types of interstitial cells of Cajal (ICC) interconnected by gap junctions and connected by close contacts to muscle layers. At the deep muscular plexus, ICC were present, not regularly close to nerve axons or in gap junction contact with one another or outer circular muscle, which had many gap junctions. Slow waves (5.2 ± 2 mV amplitude and 4.6 ± 0.7 s duration) occurred at 9.9 ± 1.1 counts/min. Tissue length and time constants were 2.00 ± 0.3 mm and 111 ± 37 ms, respectively. Large electrical field-induced hyperpolarizations or depolarizations reduced amplitudes but not frequencies or durations of slow waves; hyperpolarizations progressively reduced inhibitory junction potentials as if the K+channel opening mediated them. In conclusion, the myenteric plexus ICC of pig ileum, which appears to pace the muscle layers, appears insensitive to voltages applied to the syncytium of circular muscle cells. Limited coupling between ICC and circular muscle or voltage-insensitive pacemaking activity may explain these findings.