THE intracellular protein tyrosine kinase FAK (focal adhesion kinase) was originally identified by its high level of tyrosine phosphorylation in v-src-transformed cells(1-4). FAK Is also highly phosphorylated during early development(5,6). In cultured cells it is localized to focal adhesion contacts and becomes phosphorylated and activated in response to integrin-mediated binding of cells to the extracellular matrix, suggesting an important role in cell adhesion and/or migration. We have generated FAK-deficient mice by gene targeting to examine the role of FAK during development. Mutant embryos displayed a general defect of mesoderm development, and cells from these embryos had reduced mobility in vitro. Surprisingly, the number of focal adhesions was increased in FAK-deficient cells, suggesting that PAK may be involved in the turnover of focal adhesion contacts during cell migration.