Members of the ADAM family (membrane proteins with a disintegrin and metalloprotease domain) have been implicated in several cell-interactive events, including cell-cell fusion. Recent evidence implicates three ADAMs, fertilin-alpha, fertilin-beta, and meltrin-alpha, in sperm-egg fusion and myoblast fusion. In light of the large number and wide tissue distribution of the ADAMs, they may also participate in other cell-cell fusion events. As ADAMs are also found in both vertebrates and invertebrates, some features of cell-cell fusion reactions may be conserved throughout the animal kingdom.