Insulin receptor-related receptor (IRR), a member of the insulin receptor family, is most abundantly expressed in the kidney. However, its endogenous ligand and physiological roles are still unknown. To elucidate the physiological role of IRR, an orphan receptor, in the kidney, we examined the localization of IRR mRNA and its immunoreactivity in the rat kidney by in situ hybridization and immunohistochemistry, respectively. IRR mRNA was found to be exclusively localized in the cortical collecting duct. The localization of IRR immunoreactivity was consistent with that of IRR mRNA. Furthermore, IRR immunoreactivity was found to be localized on the basolateral plasma membrane of the epithelial cells that were a minor cell subpopulation (20 to 30%) of the duct. The present findings indicated that IRR in the kidney was exclusively localized on the basolateral plasma membrane of type B intercalated cells of the cortical collecting duct.