Serial crossover tests were carried out on 10 to 15 large, trained, male dogs that were moderately deeply anaesthetized for 90 minutes, at two-week intervals, with thiopental, Innovar, diethyl ether cyclopropane, chloroform, trichlorethylene, fluroxene, halothane, halothane-ether azeotrope, and methoxyflurane. These tests were done under four conditions: spontaneous breathing with 50 per cent N2O + 50 per cent O2 unless apnoea became imminent (chloroform-usual, cyclopropane-occasional, Innovar-briefly); controlled breathing with 50 per cent N2O + 50 per cent O2; controlled breathing with 85 per cent N2O + 15 per cent O2; and controlled breathing with 50 per cent N2O + 47.5 per cent O2 + 2.5 per cent CO2. Anaesthesia was induced in all experiments with 20 mg./kg. thiopental. Cyclopropane was administered with 70 per cent oxygen in a closed-circle system with an absorber under the first two conditions only. The remaining inhalation agents were administered in a non-rebreathing system. Thiopental and Innovar were administered intravenously by drip infusion for one hour. Blood assays of histamine, serotonin, epinephrine, and norepinephrine were carried out at the beginning and end of each test along with measurements of the pH,\(P_{aCO_2 } ,P_{aO_2 } \), haematocrit, SGOT, SGPT, lactate, pyruvate, blood water, sugar, potassium, and inorganic phosphorus. Volume of blood withdrawn for the tests was replaced with 0.9 per cent saline. During each test, mean arterial blood pressure was measured directly from the femoral artery; breathing rate and volume were monitored with a respirometer during spontaneous breathing or regulated at 350 to 400 ml./kg./min. during controlled breathing; heart rate and rhythm were monitored and recorded from E.C.G. (lead 2), and urine excretion was monitored and recorded by gravity drainage with a catheter attached to a calibrated trap bottle. All data were analyzed statistically. The following effects were noted: 1. Thiopental usually caused a rise in the catecholamines, but no hypotension or oliguria; 2. Innovar usually caused a rise in blood sugar, hypotension and oliguria; elevation of catecholamines was inconsistent; 3. Diethyl ether caused metabolic acidosis, haemoconcentration, water loss, hyperglycaemia, excess lactate, elevation of catecholamines and oliguria, but no hypotension; 4. Cyclopropane caused hypercapnoea (during spontaneous respiration) and oliguria, but no hypotension; catecholamines rose slightly; 5. Chloroform caused slight hyperglycaemia and oliguria; 6. Trichlorethylene caused ollguria and a rise in serotonin when CO2 was administered; 7. Fluroxene caused hyperglycaemia and elevated lactate and pyruvate during spontaneous breathing, a rise in the catecholamines during mild hypoxia, and oliguria; 8. Halothane, halothane-ether azeotrope, and methoxyflurane caused hypotension and oliguria, but no consistent metabolic changes. It was evident that diethyl ether caused the most obvious metabolic disturbances, and these were usually accompanied by a rise in the catecholamines. There were virtually no consistent or appreciable changes in the histamine or serotonin assays. Theoretically, it is possible that alterations in the latter two biogenic amines might have occurred to a greater extent than the reported values indicate, since it is possible that they were released and then were taken up rapidly by the tissues or receptors of the effector organs or broken down metabolically. For that matter, catecholamines released into the blood during anaesthesia with some agents (the halogenated agents and cyclopropane) may have had the same fate, whereas with diethyl ether they remained in the bloodstream. However, it is unlikely that this occurred, for if it had, there might have been less likelihood of hypotension, at least with the more potent halogenated anaesthetics. It is important to keep in mind also that when considering the percentage changes in these biogenic amines one takes a distorted view, particularly with respect to the catecholamine values, because the assay method involves technical errors of such a magnitude that when the amount measured is near zero, or near the lower limit of detectability (as was observed with many of the control values of epinephrine), it is difficult to accept as significant those changes that appear large during an experiment.