Repulsive guidance molecules (RGMs) are recently identified proteins implicated in neuronal differentiation, migration, and apoptosis. However, in non-neural tissues a specific biological function of RGM is still unknown. In this study, we describe the expression patterns of the RGM members (a, b, and c) during embryonic and postnatal development of the small and large murine intestine. We demonstrated by RT-PCR, in situ hybridization, Western blot, and immunocytochemistry that subtypes RGMa and RGMb but not RGMc were strongly expressed in enteric ganglia cells of the fetal and adult gut. In contrast to the enteric nervous system, RGMa and RGMb expression in the intestinal epithelium started during postnatal gut development. Interestingly, both subtypes were predominantly expressed in the proliferative crypt compartment of the gut epithelium and in paneth cells of small intestine. The development-dependent expression in enteric ganglia and intestinal epithelial cells suggests that RGM may be involved in cell migration, differentiation, and apoptosis with similar cellular mechanisms as described in the central nervous system. Developmental Dynamics 234:169–175, 2005. © 2005 Wiley-Liss, Inc.