The problems of anesthetic drug action will be attacked in human, animal, and in vitro studies. Twenty-two investigators form seven interrelated teams working in four major areas: circulation, nerve and muscle, respiration, and neurophysiology. (1) Circulation: Dr. Bagshaw will study anesthetic effects on mechanisms of blood pressure control; regional and total vascular impedance will be determined at different levels of halothane and chloralose anesthesia. Another group (Drs. Wollman, Aidinis, Harp, Kennell and Shapiro) will study regional cerebral blood flow and cerebral metabolism during acid-base changes, hypotension, and head trauma. The protective effects of barbiturates and hypocapnia will be measured. (2) Nerve and muscle investigations (Drs. Strobel, Rosenberg and Levitt) will include in vitro effects of anesthetics on metabolism, enzymes, and mechanics of skeletal muscle, myocardium, and synaptosomes. Caffeine-induced contracture of frog and mammalian muscle will be used as a model of malignant hyperthermia. (3) In the respiratory area, one group (Drs. Edwards and Davies) will study chemoreceptor effects on medullary neurophysiology. A pulmonary pathophysiology group (Drs. Marshall, Aukburg, Geer, Klineberg, Neufeld, Soma, and Wyche) will measure anesthetic effects on lung capillary permeability, extravascular water, and bronchial circulation. Multiple indicator dilution studies will allow simultaneous measurement of capillary permeability to several compounds. The function of the reticuloendothelial system in the removal of fibrin microaggregates after blood transfusion will be studied. Another group (Drs. Smith and Keykhah) will investigate interactions of drugs, especially opioids and anesthetics, on respiration. (4) Neurophysiology: Dr. Clark will continue studies of thermo-regulation following decerebration, and collateral circulation between cerebral arteries. Investigators are supported by an analytical chemistry laboratory (Dr. Behar) and other shared core facilities including major equipment and a well-equipped electronics laboratory.