Electrical rhythmicity in the gastrointestinal tract may originate in interstitial cells of Cajal (IC). Development of IC in the small intestine is linked to signaling via the tyrosine kinase receptor, c-kit. IC express c-kit protein, and disruption of c-kit signaling causes breakdown in IC networks and loss of slow waves. We tested whether mutations in steel factor, the ligand for c-kit, affect the development of IC networks. IC were found in the region of the myenteric plexus (IC-MY) in mice with steel mutations (i.e., Sl/Sld) at 5-10 days postpartum, but these cells formed an abnormal network. IC-MY were not observed in adult Sl/Sld animals. IC in the deep muscular plexus (IC-DMP) appeared normal in Sl/Sld animals. Electrical slow waves, normally present in the small intestine, were absent in Sl/Sld animals (10-30 days postpartum). Neural inputs were intact in Sl/Sld animals. Steel factor appears important for the development of certain classes of IC, and IC-MY appear to be involved in the generation of electrical rhythmicity in the small intestine.