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The role of histamine, catecholamines, and serotonin was investigated in the early phase of endotoxin shock. Histamine induced hemodynamic alterations similar to indotoxin; however, these changes could also be induced by larger amounts of acetylcholine. Plasma concentrations of histamine were not elevated by sublethal amounts of endotoxin, and vascular responsiveness to histamine was reduced during endotoxemia. Pretreatment with compound 48/80 failed to alter responses to endotoxin. Epinephrine concentrations increased, and arterial sensitivity to epinephrine was enhanced during endotoxemia. Pretreatment with reserpine, however, did not alter the events of endotoxin shock, and infusions of catecholamines incompletely duplicated the responses to endotoxin. During endotoxemia plasma serotonin concentrations were reduced, and arterial sensitivity to serotonin was heightened. Replacement of serotonin during endotoxin shock failed to alter the events induced by endotoxin. (Author)