The responsiveness of the smallest blood vessels of the human skin was measured in systemic anoxemia, hypercapnia, acidosis, and alkalosis. A method was used which measured quantitatively the reactive hyperemia produced by a standardized period of local ischemia of these fine vessels. By timing the clearing period of the threshold hyperemia response a direct indication of blood flow in these fine vessels was obtained. The following conclusions were reached concerning the responses of the smallest blood vessels of the skin.

1. Systemic anoxemia causes a decrease in sensitivity to local ischemia and a slowing of the blood flow.

2. Hypercapnia prevents the changes resulting from anoxemia.

3. These changes in the smallest blood vessels of the skin occur independently of changes in pulse rate, blood pressure, and respiratory rate and depth.

4. With systemic acidosis there is a decrease in sensitivity to local ischemia and a slowing of blood flow. The exact opposite takes place in systemic alkalosis.

5. The view is advanced, after due consideration of the facts, that the carbon dioxide concentration of the blood, or something directly associated with it, is the most important factor determining the sensitivity of these vessels, rather than oxygen saturation or changes in blood pH.

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