Proinflammatory cytokine tumor necrosis factor-alpha (TNF-a) contributes to a variety of inflammatory responses and programmed cell death. Notch receptor and its ligand participate in cell fate decisions during vertebrate development and are associated with several human disorders, including a T-cell lymphoma. TNF-a, notch and its ligand delta are all membrane-bond molecules, which are cleaved by proteases to release mature proteins or functional receptor. ADAM10, a metalloprotease-disintegrin in the family of mammalian ADAM (for a disintegrin and metalloprotease), was recently identified to cleave TNF-a, notch and its ligand delta (1-3). The genes encoding human, mouse, and bovine ADAM10 were recently cloned and designated ADAM 10, kuzbanian (KUZ), and MADM, respectively, (1,2,4). ADAM10 mRNA is expressed in a variety of human and bovine tissues (1,4).