The decline in renal function seen in a variety of pathological states is associated with an increase in the number and changes in the protein synthetic activity of tubular interstitial cells. However, the relationship between expansion of the interstitial compartment (interstitial fibrosis) and loss of renal epithelial tubules and capillaries remains unclear. Interstitial pathologies accompanying renal failure may merely be coincident with tubular degeneration. Alternatively, interstitial pathologies may cause tubular degeneration. Finally, it is possible that “pathological” changes in the interstitial compartment reflect the kidney’s attempts to repair damaged tubules. Discriminating among these possibilities has been difficult, in part because the function of interstitial cells in the healthy kidney remains poorly understood. A new study by Iwano et al. in this issue of the JCI (1) suggests that recent advances in the field of kidney development may provide insight into this important clinical problem.