The functional correlates of structural remodelling of the preplacental arteries are not well known. We examined the responses of these vessels to vasoactive agents in guinea pigs at mid and late gestation, and attempted to relate them to changes in vessel structure. Segments were taken from the arcade artery, a mesometrial artery near its origin, and an artery near the placenta. They were mounted as rings in a myograph and concentration-response curves were obtained for U46619, endothelin-1 and arginine vasopressin. The vessel segments were then examined by histology and immunohistochemistry. Trophoblast was identified as immunopositive for cytokeratin, circular muscle stained positive for muscle actin and smooth muscle actin, and presumed myofibroblasts in the adventitial layer stained positive only for smooth muscle actin. At both gestational ages, arcade and mesometrial arteries had intact vessel walls. Midgestation placental arteries were characterized by partial or complete disruption of the internal elastic lamina and the presence of a large number of myofibroblasts and of periarterial trophoblast. In late pregnancy, the changes were more extensive, with almost complete dedifferentiation of the smooth muscle cells and trophoblast invasion of the adventitial layer. From midgestation to late gestation, the responses of placental arteries to U46619, endothelin-1 and arginine vasopressin, normalized to the response to K+ depolarization, were significantly reduced. This suggests that the extensive changes in wall structure in late gestation, which accompany trophoblast invasion, modulate the responses of these vessels to vasoconstrictors. However, mesometrial arteries also demonstrated reduced responsiveness to U46619, suggesting the influence of factors other than trophoblast.