The membrane-type matrix metalloproteinases (MT-MMPs) are a subclass of the matrix metalloproteinase (MMP) family which uniquely possess a C-terminal transmembrane domain and are initiators of an activation cascade for progelatinase A (MMP-2). Recent studies have shown that they can also efficiently directly degrade a number of matrix macromolecules. We now show that cells expressing MT1-MMP on their cell surfaces cause subjacent proteolysis of a gelatin film and that this proteolysis is inhibited by TIMP-2 but not by TIMP-1. These data indicate that expression of MT1-MMP on the cell surface may lead to both progelatinase A activation and extracellular matrix degradation.