The effect of hemoglobin oxygen saturation upon blood flow through the hind leg of the dog was studied by perfusing the femoral arteries of five normal dogs with blood, the oxygen saturation of which was varied between 100% and 0%, and by perfusing the femoral arteries of nine spinal animals with blood, the oxygen saturation of which was varied between 100% and 10%. The blood saturation was controlled in the following manner: The blood was obtained from the lower lobe of the left lung as it was respired with a mixture of nitrogen and oxygen. By varying the ratio of the mixture, the blood oxygen saturation could be controlled exactly. Decreasing the oxygen saturation stepwise caused a correlated increase in blood flow through the leg. The results have shown that blood flow in the nonspinal dogs increased to an average of 3.4 times the normal value as oxygen saturation fell from 100% to 0%. In the spinal dogs blood flow increased to an average of 3.1 times normal as oxygen saturation fell from 100% to 10%. These experiments demonstrate that the local tissues can autoregulate their blood flow to help maintain an adequate supply of oxygen.