gp46 is a collagen-binding heat-shock glycoprotein with a possible role in the biosynthesis of collagen as well as in cell differentiation and fusion. In this study, the relative levels of gp46 protein and its mRNA transcript were examined, as well as the mRNA levels of collagen types I and IV in first trimester and term human placental tissues. Western blot analysis revealed substantially higher levels of gp46 in first trimester placentae than in term placentae. Similarly, elevated levels of type IV collagen transcript were detected in first trimester relative to term issues. Interestingly, the levels of gp46 and type I collagen mRNA remained unchanged. Immunohistochemical analysis of first trimester tissues demonstrated intense gp46 staining in mononucleated villous and extravillous cytotrophoblasts, decidual cells and in the villous connective tissue stroma. Syncytiotrophoblast in the same tissues also exhibited gp46 staining but at a reduced intensity. In chronic villi of term placentae, faint gp46 staining was only observed in the syncytiotrophoblast layer. However, as in the first trimester placentae, intense labelling was evident in the extravillous cytotrophoblasts and decidual cells of these tissues. These results suggest a developmental regulation of gp46 expression at the fetal-maternal interface during pregnancy and suggest a possible functional link between gp46 and collagen type IV. during gestation.