The umbilical artery was chosen as a possible model for evaluating the vascular injury provoked by tobacco smoking in humans. Cords from newborn children delivered by 15 nonsmoking and 13 smoking mothers were studied in the transmission and the scanning electron microscope. Pronounced intimal changes were seen in the arteries from smoking mothers; the most important findings were degenerative changes of the endothelium such as swelling, blebbing, contraction, and subsequent opening of the endothelial junctions with formation of subendothelial edema. Other observations included dilation of the endoplasmic reticulum in the endothelium and reparative changes such as a considerable widening of the basement membrane. Since similar changes can be induced in arteries of animals by exposure to carbon monoxide or perfusion with nicotine, we conclude that the present study supports the concept that tobacco smoking is harmful to the vascular endothelium. This study also contributes to an understanding of the mechanism through which vascular injury is provoked in heavy smokers.