The involvement of endovascular trophoblast in fibrinoid deposition, replacement of the endothelium and vascular smooth muscle breakdown is studied in spiral arteries of the mesometrial triangle from day 15 to day 21 of rat pregnancy, by examining arterial cross sections after staining for cytokeratin, PAS, CD31 and alpha-actin. From day 15 to day 18 of pregnancy, fibrinoid deposition underneath the endovascular trophoblast increases gradually, whereas the amount of endovascular trophoblast in invaded arteries remains constant. CD31 staining is significantly reduced in sub-ET (= underlying the endovascular trophoblast) as compared to extra-ET (= outside the endovascular trophoblast) and no-ET (= non-invaded arterial sections) at each time-point of pregnancy examined (P < 0.005 and P < 0.0005 at each day of pregnancy), whereas alpha-actin staining is reduced both in sub-ET and in extra-ET as compared to no-ET. During pregnancy, CD31 staining in sub-ET initially declines, but increases significantly on day 21 (P < 0.001 versus d20) suggesting re-endothelialization of the vascular wall. In conclusion, changes in spiral arteries of pregnant rats reveal striking similarities with physiological changes seen in human pregnancy, thus emphasizing the usefulness of this species as an experimental model for studying normal and complicated pregnancies in humans.