A scanning and transmission electron microscope study of canine jugular and femoral veins revealed that large numbers of white cells adhered to the vessel walls, passed through the endothelial intercellular junctions and accumulated in pockets between the endothelium and basement membrane. This led to extensive separation and desquamation of endothelial cells with exposure of subendothelial structures in many areas. The white cell invasion was caused by surgical trauma to adjacent tissues (rather than to the vessel itself) followed by 1 or 7 minutes occlusion by pressure applied externally just below the areas of dissection. The invasion was blocked by lidocaine (Xylocaine), an agent known to inhibit white cell migration. However, white cell invasion occurred when veins in lidocaine-treated dogs were perfused with normal blood. No white cell invasion occurred in dogs made neutropenic with vinblastine but did occur when these veins were perfused with normal blood.