Plasma catecholamine levels were studied during general anaesthesia with diethyl ether, cyclopropane, and halothane in dogs and human subjects. Anaesthesia with ether/oxygen caused highly significant increases in plasma noradrenaline in dogs and man. The response was less marked in man, but a significant direct correlation could be established (in a small number of patients) between the rise in plasma noradrenaline and blood ether concentrations during ether anaesthesia without surgical interference. Plasma adrenaline was also significantly increased in dogs during ether anaesthesia, and in man to a lesser extent; highly significant rises were measured during surgery in man. The severe metabolic acidosis induced by diethyl ether in the dog bore a direct relationship to circulating catecholamine concentration and was greatly reduced by bilateral adrenalectomy. A mild but definite metabolic acidosis was measured during nitrous oxide/ oxygen/ether and ether/oxygen anaesthesia in man. In adrenalectomized dogs, variable moderate rises in plasma noradrenaline were measured during ether anaesthesia, from which it is inferred that in this species the rise in plasma noradrenaline stems partly from extra-adrenal areas. Since hypercarbia superimposed on ether anaesthesia in adrenalectomized dogs caused further increases in plasma noradrenaline, it is considered that the extra-adrenal sympathetic excitation induced by ether is submaximal.