Vision is as necessary an element in scientific achievement as is the carefully controlled experiment.-Ernest Gellhorn, 1953 SOME OF TIIE NEUROENDOCRINE SUBSTANCES that play a prominent role in the central nervous system are found in the peripheral circulation. Their exact functions are not entirely clear, but it appears evident that alterations in their concentration in the circulating blood are associated with profound overt mental and physical changes, TM as well as possibly initiating sudden serious disturbances of pulmonary ventilation, myocardial contractility, microcireulatory homeostasis, gastrointestinal and renal function, and carbohydrate metabolism. ~-9 These in turn may lead to the development of a shock-like state and death. The purpose of this study was to make a precise systematic inquh T into the effects of general anaesthetics as administered in clinical practice on the circulating blood level of four biogenic amines and to attempt to interrelate these with any changes that might appear in the mean arterial blood pressure, urine output , haematocrit, blood water, blood sugar, serum potassium, serum inorganic phosphorus, pyruvate, lactate, oxygen tension, acid-base balance, and serum transaminases (SGOT and SGPT). MATERIALS ANn METHODS Serial crossover tests were carried out in four consecutive sets of experiments in 10 to 15 trained, large (20 to 30 kg.) male dogs. Each animal received a general anaesthetic at one-to two-week intervals without prior administration of premedicant drugs or antisialogogues. After an overnight fast, a dog was weighed, then an intravenous infusion of 0.9 per cent saline was started in a forepaw vein after drawing a blood sample for estimation of blood sugar, serum potassium, serum inorganic phosphorus, SCOT, SGPT, whole blood histamine, and serotonin and plasma catecholamines (epinephrine and norepinephrine). Anaesthesia was then induced with 20 mg./kg, thiopenta] (2.S$ solution), and the dog was intubated with a large cuffed tube that was attached to a gas machine which delivered NsO ~ O~ (except with cyclopropane, when N20 was not used). A gas flow was used sufllcient to provide a minute ventilation of 350 to 400 ml./kg.