The canine abdominal aorta and vena cava were examined 6 months after single doses of intraoperatively delivered electrons (IORT), fractionated external beam X rays, or a combination. The predominant pathologic change in aortas given fractionated doses was a segmental thickening of the subendothelial region of the tunica intima which was due to fibroelastic proliferation. In severe cases, the intimal proliferation caused significant narrowing of the aortic lumen. The greatest proliferation and lumen narrowing resulted from 80 Gy given in 30 fractions, whereas 60 Gy produced little response. In contrast, IORT alone or combined with fractionated doses resulted in mild subendothelial intimal proliferation at all doses. In some aortas there was focal aortic wall thinning after IORT alone or combined with fractionated doses. This response may be explained by increased intimal cell death and lost or delayed proliferative capability caused by large single doses. These studies suggest that large single doses produce structural alterations in the walls of large blood vessels that are clinically undetectable at early post-irradiation times. If these changes progress in severity they could lead to late effects such as rupture, fissure, or aneurysm that are clinically more significant than the marked intimal proliferation and lumen narrowing changes seen after fractionated doses. The aortic cell responsible for intimal fibroelastic proliferation appears to be a pluripotential stem cell capable of producing fibrous, elastic, and possibly smooth muscle tissue. There were no significant alterations in any of the irradiated vena cavas.