Molecular and biochemical studies have made substantial contributions to the understanding of metalloproteinases (MPs) and their natural inhibitor TIMP (tissue inhibitor of metalloproteinases) but knowledge of their specific roles in tissue breakdown in vivo is still meagre. A major problem is that there are few techniques available that can detect small amounts of these entities at the sites of resorption. One approach to this problem is to prepare specific polyclonal antisera for use in immunolocalization studies on cells and tissues ex vivo. Another is to develop model systems of rapid matrix destruction. Examples of these techniques are presented and discussed in relation to other studies. In many situations unique patterns of synthesis have been observed, consistent with specific roles for the individual MPs and biochemical data. Active collagenase can be localized to extracellular components in tissues where rapid destruction is taking place. Thus both approaches are proving invaluable in defining the roles of MPs and TIMP in normal and pathological situations.