We describe the isolation of a novel protein from the conditioned medium of human articular cartilage chondrocytes in primary culture, This 39-kDa protein has the N-terminal sequence YKL, which we have termed YKL-39, The 1434-nucleotide sequence of the YKL-39 cDNA predicts a 385-residue initial translation product and a 364-residue mature YKL-39, The amino acid sequence of YKL-39 is most closely related to YKL-40, followed by macrophage chitotriosidase, oviductal glycoprotein, and macrophage YM-1, All five proteins share significant sequence identity with bacterial chitinases and have the probable structure of an (alpha beta)(8) barrel, YKL-39 lacks the active site glutamate, which is essential for the activity of chitinases, and as expected has no chitinase activity, The highest level of YKL-39 mRNA expression is seen in chondrocytes, followed by synoviocytes, lung, and heart, YKL-39 accounts for 4% of the protein in chondrocyte-conditioned medium, prostromelysin accounts for 17%, and YKL-40 accounts for 33%, In contrast to YKL-40, YRL-39 is not a glycoprotein and does not bind to heparin.