Mesenchymal-epithelial interactions are important for many biological processes in epithelial organs such as the kidney. Hepatocyte growth factor (HGF) is a mesenchymally derived polypeptide cytokine that acts through its tyrosine kinase c-met receptor and is an important mediator of these interactions. This article reviews data showing the in vitro actions of HGF on renal epithelial cells that result in such diverse responses as mitogenesis, motogenesis, and morphogenesis. It also examines the in vivo evidence linking HGF and the c-met receptor to kidney development, regeneration following injury, and renal disease. Elucidating cellular mechanisms underlying the coordinated control of diverse HGF-induced phenotypic changes in renal epithelia in vitro should contribute to a clearer understanding of complex biological processes such as organogenesis, regeneration, and carcinogenesis in epithelial organs such as the kidney. Copyright © 1999 by Academic Press. All rights of reproduction in any form reserved.