Insulin-like growth factor-I (IGF-I) modulates renal function, growth, and repair. IGF-I produced in the kidney is one component of the intrarenal IGF-I system comprising the IGF-I receptor (IGF-IR) and six IGF-binding proteins (IGFBP). Because of the physiologic importance of IGF-I and its potential therapeutic properties, the renal sites of mRNA synthesis for IGF-I, IGF-IR, and IGFBP-I through IGFBP-5 were characterized in rat kidney by in situ hybridization. Anatomical heterogeneity was prominent. IGF-I mRNA was present in the thick ascending limb of Henle in the outer medulla, whereas IGF-IR mRNA was diffusely present at low levels throughout the kidney. IGFBP-I mRNA was localized to cells within the distal convoluted tubules as well as the thick ascending limb of Henle. IGFBP-2 mRNA was expressed in glomeruli, medullary ray collecting ducts, pelvic smooth muscle and uroepithelium, and the papilla tip; IGFBP-3 mRNA was localized to the cortical interstitium, whereas IGFBP-4 mRNA was expressed in proximal tubules, medullary ray collecting ducts, and glomeruli. IGFBP-5 was strongly positive throughout the medulla with lesser expression in the distal convoluted tubules and glomeruli. This study highlights the complexity of the intrarenal IGF-I system. The striking heterogeneity of IGFBP gene expression suggests that the various IGFBP may have diverse modulatory effects on the action of IGF-I or discrete effects of their own.