AbstractDuring implantation, a balance of factors regulates the invasive properties of the embryo and the anti‐invasive properties of uterine decidua. Although antiproteinases such as the metalloproteinase inhibitor TIMP‐3 are thought to play critical roles in preventing the overaggressive invasion of trophoblasts, the mechanism of antiproteinase regulation is unknown. Recently, the prohormone convertase SPC‐6 has been found to be co‐expressed in embryo‐proximal decidua in association with TIMP‐3. As members of this serine proteinase family are known to activate latent TGFβ family members which regulate decidual TIMP‐3 levels, we sought to characterize the expression of SPC‐6 during pregnancy and artificial decidualization. In this study, we demonstrate that the zone of SPC‐6 gene expression exhibits a great degree of temporal and spatial overlap with TIMP‐3 gene expression in uterine decidua from E5.5 through to E8.5. Like TIMP‐3, we demonstrate that SPC‐6 expression is induced during the decidual cell response using an in vivo model of artificial decidualization. Both the secreted and membrane bound forms of SPC‐6 are expressed throughout the period of decidualization, suggesting that SPC‐6 may play multiple roles during this developmental period. This is confirmed by our observation of the movement of SPC‐6 expression to the presumptive placental region, as TIMP‐3 expression regresses at the implantation site. Mol. Reprod. Dev. 61:453–459, 2002. © 2002 Wiley‐Liss, Inc.