The effect was investigated of ether, cyclopropane, thiopentone and certain relaxant agents on the cardiac output as estimated by the Heart-Lung Preparation in dogs. Measurements were made of cardiac output and forearm blood-flow (a) in 15 patients anæsthetized with thiopentone, nitrous oxide, oxygen and d-tubocurarine chloride; (b) in 10 patients anaesthetized with thiopentone, nitrous oxide, oxygen and ether, and (c) in 6 patients anæsthetized with thiopentone and cyclopropane. Cardiac output was estimated by cardiac catheterization, the Fick Principle being employed. In the dog ether, cyclopropane and thiopentone were potent myocardial poisons, but in the intact human subject, in the case of those anæsthetized with ether and cyclopropane, the initial response was a transient increase in cardiac output and forearm blood-flow. This was absent in those cases anæsthetized with thiopentone, nitrous oxide and d-tubocurarine chloride, in whom there was little change. The mechanisms which might underlie these changes are discussed. In the Appendix the accuracy of determinations of cardiac output by the Fick Principle in anæsthetized patients is discussed and accuracy of the methods employed in the present estimations indicated.