The matrix metalloproteinases (MMPs) are a large multigene family of over 24 secreted and cell surface enzymes that process or degrade numerous extracellular or pericellular substrates. Their targets include nearly all extracellular matrix (ECM) components, other proteinases, proteinase inhibitors, clotting factors, growth factors, cell surface receptors, and cell–cell adhesion molecules (Yong et al., 2001). MMPs play a role in many cellular activities, including morphogenesis, survival, angiogenesis, inflammation, wound healing, and signaling (Sternlicht and Werb, 2001). Much of the information known about their biology has come from studies in vitro. A major challenge in understanding the biology of MMPs is the identification of their function in vivo. To date, little is known concerning the distribution and/or role of MMPs in developing organisms. Knockouts of MMPs and their natural inhibitors, the TIMPs, in mice have suggested that some MMPs have important developmental roles, for instance, MMP-9 and MMP-14 in skeletal development (Vu et al., 1998; Holmbeck et al., 1999). However, others show little or no phenotype possibly due to functional redundancy between family members. Studies in other organisms such as chick, zebrafish, Xenopus, and Drosophila have suggested that MMPs play an important role in tissue morphogenesis during development (Cai and Brauer, 2002; Jung et al., 2002; Zhang et al., 2003c; Page-McCaw et al., 2003). In fact, the first collagenase activity identified was from studies on tadpole tail resorption during metamorphosis (Gross and Lapiere, 1962). In Xenopus several MMPs have been cloned as seen in Figure 2 (Patterton et al., 1995; Stolow et al., 1996; Yang et al., 1997; Carinato et al., 2000; Jung et al., 2002). Most of the work looking at their function has concentrated on their role in tadpole tail resorption and other aspects of metamorphosis (Berry et al., 1998; Damjanovski et al., 2000, 2001; Jung et al., 2002). Of the Xenopus MMPs cloned to date, only ST3 (MMP-11), Col3 (MMP-13), and MMP-9 have been shown to be expressed early in development (Carinato et al., 2000; Damjanovski et al., 2000). Damjanovski et al. (2001) have carried out overexpression experiments using Xenopus transgenics in which they expressed ST3, Col4 (MMP-18) and mouse MT-MMP5 (MMP-24) during Xenopus development using the CMV promoter. All three led to lethality during late embryonic development. Other than these experiments, very little is known about the function of Xenopus MMPs during early development. We have begun to look at the role MMPs play during Xenopus embryogenesis. We present here the expression patterns of three new Xenopus MMP genes and show them to be expressed at different times during development and in restricted patterns in the neural crest, ventral ectoderm, and early myeloid/macrophage cells.