The extracellular matrix proteolytic machinery is known to play a major role in trophoblast invasion, a process that shares similar features with the pathology of tumor invasion. In this study we investigated the expression of the recently described membrane-type matrix metalloproteinase-1 (MT-MMP-1; MMP-14) in early human placenta and decidual membrane to determine whether it might play a role in invasion. With in situ hybridization, the cytotrophoblasts of trophoblastic columns and the infiltrating intermediate trophoblasts in the decidual membrane were found to be the main producers of MT-MMP-1 mRNA. Gene expression was also seen in the villous double-layered trophoblastic epithelium and in the decidual cells of the decidual membrane. In endothelial and fibroblastic cells, however, the hybridization signal was either very weak or nonexistent. Immunohistochemical analysis and immunoelectron microscopy correlated well with the in situ hybridization findings. The most significant exception to this consisted of pericytes of spiral arteries, which appeared to lack MT-MMP-1 mRNA but showed intensive intracytoplasmic staining for the antigen. Our results show that MT-MMP-1 mRNA production is highly characteristic of intermediate trophoblasts, and MT-MMP-1 may have general importance in the tissue organization of early human placenta. We propose that MT-MMP-1 could be one of the key enzymes in the process of trophoblast invasion, acting alone or as a cell-surface activator of other proteinases.