Intracellular recordings have been made in vitro from the myenteric neurons of the distal colon of normal littermates of the piebald-lethal mouse. Out of a total of 90 neurons, 82 were classified as S/type 1 cells and 8 as AH/type 2 cells. Seventy-eight out of 82 S cells showed spontaneous fast excitatory postsynaptic potentials (EPSPs) sensitive to d-tubocurarine (dTC, 280 microM), and 22 S cells showed spontaneous action potentials (APs). Six S cells and 1 AH cell showed spontaneous nonnicotinic slow depolarizations associated with an increase in the input resistance of the cells; during the spontaneous slow depolarization in the S cells there was an increase in the frequency of nicotinic fast EPSPs and APs. Three S cells showed spontaneously occurring regular oscillations of the membrane potential (approximately mV in amplitude and approximately 4/min). Transmural nerve stimulation produced fast EPSPs with a wide range of latencies (3 ms to 20 s) in S cells; the fast EPSPs were blocked by dTC (280 microM) or solutions containing low Ca2+ (0.25 mM) and high Mg2+ (12 mM) but not by atropine (ATR, 14 microM). Single or repetitive transmural stimulation produced slow EPSPs in 24 S cells and 3 AH cells; these were not blocked by dTC (280 microM) nor ATR (14 microM). During the slow EPSPs there was an increase in the input resistance of the cells. In those S cells that showed slow EPSPs there were many long-latency fast EPSPs; long-latency fast EPSPs were also observed in 11 other S cells that did not show a slow EPSP following repetitive transmural nerve stimulation. Long-latency fast EPSPs may be related to the firing of other neurons during their slow EPSPs. The myenteric neurons in the mouse colon have similar properties to the myenteric neurons in the guinea pig small intestine. However, the colonic myenteric neurons show more ongoing synaptic activity and more prolonged activity after nerve stimulation than myenteric neurons in the guinea pig small intestine. This activity may be due to regional differences, species differences, or preparation differences (in this study the myenteric plexus was adherent to the underlying circular muscle layer).