Gelatinase B is potently inhibited by peptide hydroxamates, including molecules that have a Rt' group which is larger than the side chains of the natural amino acids.The matrix metalloproteinases (MMPs) are a family of homologous enzymes whose substrates are molecules of the extracellular matrix) The MMPs are postulated to have a major role in normal and pathological matrix turnover, and are targets of therapeutic inhibitor design) Gelatinases A (72 kDa) and B (92 kDa) are a subgroup of the MMP family whose macromolecular substrates include proteins such as gelatin, elastin, and collagens type IV and V. The specifity of the gelatinases for peptide substrates is similar to that of the interstitial collagenases and stromelysin. 3 As secreted from cells, latent gelatinase is complexed to a molecule of TIMP: gelatinase A with TIMP-2 and gelatinase B with TIMP-1. Upon activation, the gelatinases can be inhibited by binding a second molecule of TIMP. A TIMP-free form of gelatinase B is found in the specific granules of polymorphonuclear leukocytes (PMNs), and this was the source ofgelatinase B in this study. 4The gelatinases are expressed by a number of transformed cells, and their role in tumor invasion and metastasis is an area of intense interest. 5'6 Recently, gelatinase B was shown to be expressed at high levels in human osteoclasts, which suggests a role in bone remodelling. 7In this report, we show that hydroxamate inhibitors that are known to be potent inhibitors of other MMPs are also potent inhibitors ofgelatinase B.