We have cloned and characterized a cDNA encoding Cg-TIMP, the first tissue inhibitor of metalloproteinase identified in mollusks. The isolated cDNA encodes a protein of 221 residues that has a domain organization similar to that of vertebrate TIMPs including a signal sequence, and the 12 cysteines characteristic of the TIMP signature. Analysis of Cg-TIMP expression in adult oyster tissues, by Northern blot and in situ hybridization, indicates that Cg-TIMP was only expressed in hemocytes which are the key components of defense mechanisms in mollusks. We also observed that Cg-TIMP mRNA accumulated during shell damage and bacterial challenge. This pattern of expression suggests that Cg-TIMP may be an important factor in wound healing and defense mechanisms.