Analyses of platelet-derived growth factor (PDGF) and PDGF-receptor knockout mice show that the development of specific subsets of smooth muscle cells (SMCs) depend on PDGF. Pericytes and mesangial cells failed to develop in PDGF-B deficient embryos, whereas alveolar SMCs failed to develop in PDGF-A deficient embryos. The ontogeny of pericytes and alveolar SMCs suggests a common theme in the formation of PDGF-dependent SMCs, in which PDGF-receptor positive SMC progenitors spread from proximal to distal sites along PDGF-expressing epithelial, or endothelial, tubes.