Renin-expressing cells are peculiar in that they act as differentiated cells, producing the hormone renin, while they also seem to act as progenitors for other renal cell types. As such, they may have functions independent of their ability to generate renin/angiotensin. To test this hypothesis we ablated renin-expressing cells during development by placing diphtheria toxin A chain (DTA) under control of the Ren1^d mouse renin promoter by homologous recombination in a two renin gene strain (Ren2, Ren1^d). Renin expressing cells are essentially absent from kidneys in homozygotes (DTA/DTA), which, unlike wild type mice, are unable to recruit renin expressing cells when homeostasis is threatened. In contrast, renin staining in the submandibular gland (SMG), which expresses mainly Ren2, is normal. Homozygous mice survive normally, but the kidneys are small and have morphological abnormalities: 25% of the glomeruli are hyperplastic or atrophic, tubules are dilated and atrophic and there are areas of undifferentiated cells near the atrophic glomeruli and tubules. However, in contrast to the very abnormal renal vessels found when renin angiotensin system genes are deleted, the kidney vessels in homozygotes have normal wall thickness and no decrease in lumen size. Homozygotes have severely reduced kidney and plasma renin concentrations and females have reduced blood pressure. Homozygotes have elevated BUN and potassium levels, suggestive of altered renal function. We conclude that renin cells per se are necessary for the morphological integrity of the kidney and may have a role in maintenance of normal kidney function.