Insulin receptor-related receptor (IRR) is a member of the insulin receptor family. However, its endogenous ligand and the physiological roles of IRR are unknown. To elucidate the physiological roles of IRR in the brain, we examined the expression of its mRNA in the rat brain by in situ hybridization. In contrast to the widespread expression of insulin receptor and insulin-like growth factor-1 receptor mRNAs in the brain, the expression of IRR mRNA was highly restricted to the forebrain cholinergic neurons. All the forebrain cholinergic neurons expressed IRR mRNA. The present findings indicate that IRR has a selective role in the brain for forebrain cholinergic function.