Aim: To examine the response of the insulinlike growth factor (IGF) system in the kidney during a state of extreme growth. Methods: We studied the mRNA expression of IGF-I, IGF-I receptor, and IGF-binding proteins (BP) using sensitive RNase protection assays following subcutaneous implantation of growth hormone pituitary cells (GH<sub>3</sub>) in rats. Results: Within 5 weeks, the serum GH levels increased from 18.0 ± (SE) 5.0 ng/ml in control animals to 389.8 ± 30.3 ng/ml in GH<sub>3</sub> rats (n = 5, p < 0.001). The circulating IGF-I levels were also elevated. The kidney weights increased from 0.74 ± 0.01 g in controls to 1.06 ± 0.03 g in GH<sub>3</sub> animals (n = 5, p < 0.001). Similar changes were observed at week 10. The renal IGF-I mRNA averaged 1.0 ± (SD) 0.33 relative densitometry units in controls (n = 4) and increased to 2.11 ± 0.13 relative densitometry units in GH<sub>3</sub> rats (n = 5, p < 0.001). On the other hand, mRNA for the type I IGF receptor decreased in hypersomatotropic rats. Messenger RNAs for IGFBP-1 and IGFBP-4, which have been localized to renal tubules, both decreased significantly following growth induction, while IGFBP-3, the mRNA of which has an interstitial localization, was increased at week 10. Conclusion: These data suggest that there is a dynamic relationship between tubular and interstitial compartments with regard to the IGF system in the kidney which may be important in the regulation of the cell mass.