Endotoxin (E Coli, Difco), 0.5 mg in 10 ml saline, or whole blood, was infused over a ten-minute period in the retrograde direction into a branch of a mesenteric artery in anesthetized dogs; control infusions were physiologic saline or whole blood without endotoxin. After infusion, the animal's blood was allowed to circulate through the microcirculatory field. Changes in the microcirculation were recorded by cine and still photography. After infusion of endotoxin there was coincident margination of leukocytes and thickening of endothelial cells, then formation of fibrin thrombi in small veins, followed by lyses of the thrombi and extravasation of erythrocytes. Systemic blood pressure did not fall until after endothelial cell thickening and leukocyte margination (five to 25 minutes after infusion). The mean pressure fell to between 30 and 50 mm Hg, even though the dose of endotoxin was less than 1/100 of that required to cause this blood pressure fall when given IV. It is hypothesized that intracellular hydration of endothelial cells causes increased leakage of fluids and extravasation of erythrocytes following endotoxin. If the internal volumes of hexahedron-shaped cells increase without an increase in their surface areas they must assume a more spherical shape, thereby permitting gaps to develop between adjacent cells.