Directed specification and prospective isolation of chondrogenic paraxial mesoderm progeny from human pluripotent stem (PS) cells have not yet been achieved. Here we report the successful generation of KDR(-)PDGFRalpha(+) progeny expressing paraxial mesoderm genes and the mesendoderm reporter MIXL1-GFP in a chemically defined medium containing the canonical WNT signaling activator, BMP-inhibitor, and the Nodal/Activin/TGFbeta signaling controller. Isolated (GFP(+))KDR(-)PDGFRalpha(+) mesoderm cells were sensitive to sequential addition of the three chondrogenic factors PDGF, TGFbeta and BMP. Under these conditions, the cells showed robust chondrogenic activity in micromass culture, and generated a hyaline-like translucent cartilage particle in serum-free medium. In contrast, both STRO1(+) mesenchymal stem/stromal cells from adult human marrow and mesenchymal cells spontaneously arising from hPS cells showed a relatively weaker chondrogenic response in vitro, and formed more of the fibrotic cartilage particles. Thus, hPS cell-derived KDR(-)PDGFRalpha(+ )paraxial mesoderm-like cells have potential in engineered cartilage formation and cartilage repair.