Lewis1 postulated that pain in ischemic, active muscles was brought about by the accumulation in the tissue spaces of a metabolite which he designated as "Factor P." He also indicated that Factor P was the stimulus responsible for the pain of intermittent claudication and coronary occlusion. In these syndromes the pathologic process leading to obstruction of vessels supplying blood to the active muscles was the key to the production of pain. Recent investigations of headache and backache syndromes* demonstrate that sustained skeletal muscle tension can evoke pain in the absence of pathologic involvement of either the blood vessels or the muscles. In light of evidence † indicating that tetanic contractions cause reduction in muscle blood flow, it seemed desirable to explore the hypothesis that the pain mechanisms in these syndromes were essentially those involved in the genesis of ischemic muscle pain. The following experiments concerning the relationship of skeletal