The ability of tocainide (a primary amine derivative of lidocaine, 2-amino 2, 6-propionoxylidide) to inhibit leukocyte adhesion to and invasion of canine jugular veins was investigated. Leukocyte adhesion and migration were quantitated by use of 111indium-labeled leukocytes, and the morphologic characteristics of leukocytes and vessel lumen were studied by scanning electron microscopy. The morphologic characteristics of adhering and migrating 111indium-labeled leukocytes were similar to leukocytes that had not been manipulated, thus establishing their suitability for use as a marker for flammation. Exposure of leukocytes to 200 micrograms. per ml. of tocainide in autologous plasma in vitro inhibited adhesion and migration by 68 per cent. When labeled leukocytes were returned to the donor and exposed to intravenously infused tocainide the extent of reduction in adhesion and migration depended on whether tocainide infusion was started before or after neck dissection. Inhibition was only 46 per cent when dissection and injection of 111indium-labeled leukocytes preceded the start of infusion of tocainide but was 87 per cent when tocainide infusion was started before dissection and injection of leukocytes. The plasma level ranged from 25 to 47 microM over the 3 hour, 20 minute-infusion period, being 35 to 40 microM for the last hour. Migration of leukocytes across interendothelial junctions and their accumulation between the endothelial sheet and the basement membrane caused extensive damage to the endothelial lining of these veins. This was reduced when leukocyte migration was reduced. These observations suggest that the leukocyte-induced damage occurring in some sterile inflammations might be reduced by the use of local anesthetic drugs.