The hyaluronidases (Hyals) are classes of enzymes that degrade, predominantly, hyaluronan (HA). The term “hyaluronidase” is somewhat of a misnomer since they have the limited ability to degrade chondroitin (Ch) and chondroitin sulfates (ChS), albeit at a slower rate. It is a common misconception that the bacterial Hyals have absolute specificity for HA. This is incorrect. Both bacterial1 and vertebrate enzymes degrade Ch and ChS. The plausible reason for this broader specificity is that chondroitins preceded HA in evolution. For example, the nematode, Caenorhabditis elegans, contains only Ch and no HA, with only one Hyallike sequence (unpublished observations). This is most likely a chondroitinase. It is plausible, therefore, that the vertebrate Hyals evolved originally from pre-existing chondroitinases. 1 This may explain why Hyals, recognizing their ancestral substrate, retain limited ability to also degrade Ch and ChS. The Hyals from bacteria have been well characterized, and much information is available (for representative publications, see refs 2r5). The Hyals in vertebrate tissues, on the other hand, have not been studied extensively, due to the lack of structural information. Such studies were more difficult and, therefore, more limited. In addition, vertebrate Hyals are present at exceedingly low concentrations. In human serum, eg, Hyal-1 is present at 60 ng/mL. 6 They have high specific activities that are unstable during the course of purification, requiring the constant presence of detergents and protease inhibitors for their isolation. Many of such difficulties have been overcome, and a great deal of