The Runx2/Cbfa1 transcription factor regulates a program of gene expression necessary for skeletal development. To understand signals mediating skeletal formation, we examined the in vivo spatio-temporal activity of the Runx2 P1 promoter which controls expression of the bone-related Type II isoform. Transgenic mice carrying 3 kb of Runx2 promoter fused to the lacZ gene exhibit localized promoter activity in early mesenchymal condensations shortly after the embryonic turning event. Expression in developing mesenchyme continues throughout chondrogenesis and is restricted to the axial skeleton. Our data support a function for Runx2 in establishment of the prechondrocytic skeletal primordium.