Tissue transglutaminase (tTG) expression, distribution and activity were examined in human placenta and derived cells. Immunochemical techniques and RT-PCR were used to demonstrate tTG protein and mRNA in stromal cells and trophoblast in first trimester and at term, with higher levels later in pregnancy. Decidual cells also produce tTG. The data were confirmed using primary cultures of trophoblast, fibroblasts and decidual stromal cells. Substrate incorporation studies indicated tTG activity in association with fibroblast extracellular matrix and the syncytial microvillous membrane (MVM), where several target polypeptides could be observed. tTG is a major autoantigen in Coeliac disease (CoD) which is associated with poor pregnancy outcome. tTG at the placental MVM is a plausible target of maternal autoantibody action.