The acute and chronic changes produced in canine femoral arteries by ischemia and by perfusion with D10W were examined by light and by scanning electron microscopy. Mild changes of injury characterized by medial and adventitial inflammation and an increase in intimal lining cells occur following 30 min of perfusion with return to a normal microscopic appearance within 1 wk. Perfusion for 6 h produces significant injury to the entire arterial wall, as evidenced by depletion of cells and elastin from the media, replacement with collagen and eventual fibrosis. The intimal surface is replaced by a layer of spindle cells which appear to originate in the media. The internal elastic membrane is flattened and thrombosis is prominent, particularly in areas where medial fibrosis is severe. Many of the vascular changes produced by perfusion injury may persist for 3 mo. and some may even be permanent. A period of 6 h of ischemia also produces similar but less prominent alterations in vascular morphology which return to near-normal appearance within 8 wk.