Interstitial cells of Cajal (ICC) associated with the myenteric plexus of the small intestine are crucial players in gut physiology performing pacemaker functions and directing peristalsis and segmentation. ICC have been studied after chemical isolation and under culture conditions, but concerns that these methods affect the intrinsic properties have hindered progress in our understanding of ICC. To overcome this problem, we have developed a method to obtain electrophysiological recordings from ICC in situ. The critical feature is the ability to make high resistance seals onto cells that are embedded within tissue to obtain patch clamp recordings. Our first results show a prominent presence of a chloride channel, one of the proposed ICC pacemaker channels. The developed method can be applied to auxiliary cells of the enteric nervous system such as glial cells or fibroblasts and will be ideal for the study of cell-cell communication in tissue.