The adult mammalian kidney tubule epithelium exists in a relatively dormant, slowly replicative state but has a large potential for regenerative morphogenesis following severe ischemic or toxic injury. Under selective serum-free growth conditions, which included epidermal growth factor and retinoic acid, a subpopulation of renal proximal tubule cells isolated from adult rabbit kidney were grown in cell culture. These cells possessed two important characteristics: 1) an ability to differentiate morphogenically into tubule structures when grown in three-dimensional collagen gels and 2) a high capacity for self-renewal, since cell lineage analysis with a recombinant retrovirus demonstrated that in vitro tubulogenesis arose from clonal expansion of a single cell. Thus individual cells in the adult kidney have retained the ability for kidney tubulogenesis in vitro.