There is at present no agreement as to why several organs in the body are often compromised very early after either blood and fluid loss or sepsis. Close inspection (utilizing electron microscopy) usually reveals that a great many of the endothelial cells (EC) are either destroyed, transformed, or have undergone morphological changes. Since: the intimal lining of blood vessels, i.e., EC, may be important in mediating vasodilator substances and mechanisms; and early in shock and trauma, the peripheral vasculature often over compensates and results in severe ischemia in the splanchnic tract, we wondered whether or not the ability of the arterioles of the rat mesenteric microvasculature to produce reactive hyperemic responses early after ischemia and shock might not be compromised. Although the normal response of arterioles to temporary occlusion is postocclusion hyperemia and vasodilatation, arterioles of rats subjected to bowel ischemia, circulating S. enteritidis endotoxin, or Noble Collip drum trauma exhibited marked inhibition (70-100%) of these responses early after induction of circulatory shock. We are tempted to speculate that the latter is related to the failure of EC to either produce a vasodilator substance(s) or for the released vasodilator substances (in response to the occlusion) to act appropriately on the microvascular smooth muscle cells. Our results may help to shed light on a rationale for multiple organ failure and on why vasodilator therapies often are ineffective in the treatment of circulatory shock and trauma.