The localization of insulin-like growth factor I (IGF-I, somatomedin C) was investigated in the kidney of adult rats during normal conditions and after nephrectomy, using immunocytochemical and biochemical methods. In the normal kidney, IGF-I immunoreactivity could be demonstrated mainly in cells in the medullary collecting ducts and in those parts of the thin limb of Henle's loop located in the outer medulla. During compensatory growth all parts of the collecting ducts, including those in the cortex, showed IGF-I immunoreactivity, as did cells in the entire thin limb of Henle's loop. No IGF-I immunoreactivity could be demonstrated in the proximal or distal tubules, either in the control kidney or during compensatory growth. Biochemical measurements showed a significantly higher content of IGF-I in the inner medulla than in the cortex in the normal kidney. Uninephrectomy resulted in significantly increased IGF-I content in the cortex. It is suggested that IGF-I is produced mainly in the collecting ducts and in the thin limb of Henle's loop and exerts its effect on other parts of the nephron by paracrine mechanisms.