We investigated the cells that express platelet-derived growth factor receptor alpha (PDGFR alpha) during mouse embryogenesis. PDGFR alpha expression has been identified by in situ hybridization or immunohistochemistry using polyclonal antibodies on tissue sectins. Because no immunostaining study using whole-mount specimens has been published to date, we established a new monoclonal antibody (MAb), APA5, for this purpose. Our results differed in that APA5 stained only the paraxial mesoderm, whereas other investigators concluded that most if not all mesodermal cells expressed PDGFR alpha. Moreover, we did not find PDGFR alpha expression in embryonic erythrocytes, which have been previously suggested to express PDGFR alpha. On the basis of our present results, we wish to revise the proposed PDGFR alpha expression as follows. At the pregastrulation stage, PDGFR alpha is expressed only in primitive endoderm, particularly that in the ectoplacental cone. On gastrulation, it is expressed at high levels in the paraxial mesoderm. This expression continues after its differentiation into the somite. Along with the differentiation and migration of the sclerotome, PDGFR alpha + cells begin to become distributed throughout the embryonal mesenchyme. During organogenesis, particularly intense staining is detected in regions of epithelial and mesenchymal interaction, such as the tooth bud and bronchi. In addition to mesodermal derivatives, the developing lens, apical ectodermal ridge, glial precursor, cardiac valves, and choroid plexus express PDGFR alpha. Our results with whole-mount immunostaining show that PDGFR alpha is abundantly expressed and may play important roles during embryogenesis.