We examined the level of heat shock proteins (HSPs) present in umbilical cord vessels and placenta following delivery. A 10 cm segment of fresh umbilical cord was obtained immediately after delivery and a placental biopsy was obtained following the third stage of labor. Apgar scores, cord pHs, and pertinent histories were recorded. Tissues were prepared and analyzed for HSP mRNA by in situ hybridization, Western blot, and immunohistochemistry. Sixteen patients were studied. HSP72 mRNA was selectively expressed in the vascular smooth muscle in all cord arteries and veins. This correlated with marked expression of HSP72 protein in the vascular media. Both HSP72/73 mRNA and protein expression were noted diffusely in the placenta. HSP27 protein was highly expressed in umbilical cords with lower levels present in placentas. There were no correlations between method of delivery, gestational age, Apgar score, cord pH, or fetal outcome to the magnitude or distribution of the HSP response. This is the first demonstration of HSP expression in the human maternal-fetal circulation.