The matrix metalloproteinases (MMPs) have been implicated in a number of diseases involving inflammation or cellular invasion.' GM 6001 (FIG. 1) is an inhibitor of most of these enzymes with Ki's in the low nanomolar range. Though potent in vitro, this molecule is short-lived in circulation with a half-life of a few minutes.We show here that topical GM 6001 prevents the infiltration of inflammatory cells into the alkali-burned rabbit cornea and into phorbol ester-stimulated mouse skin. It thus prevents ulceration in the former and psoriasis-like inflammation and proliferation in the latter. When given systemically it blocks the infiltration of cells into the peritoneal cavity of mice stimulated with thioglycollate. Topical administration of this drug inhibits angiogenesis in the chick chorioallantoic membrane. When given intravenously, it inhibits angiogenesis in rat corneas implanted with a pellet containing tumor extract, a process requiring penetration of vascular basement membrane by endothelial cells. Finally, systemic GM 6001 increases survival of mice in a B16-Fl0 melanoma metastasis model, presumably by inhibiting cellular invasion or tumor growth.In addition to the potential for preventing direct destruction of connective tissue