The association between metabolism of the volatile anesthetics and long-term toxicity is well established. This toxicity is frequently seen as organ damage to the liver, kidney and reproductive system. An association between cancer and anesthetic exposure has also been suggested, and recent large scale epidemiologic studies in the U.S. and U.K. indicate an increase in female cancer among exposed O.R. personnel. The likely association between exposure to the waste gases in the operating room, anesthetic metabolism, teratogenicity, and carcinogenicity is based on studies indicating that irreversible effects result from anesthetic biodegradation. Our intent is to select two commonly used anesthetics, halothane and nitrous oxide, and investigate their metabolism. It is known that exposure to compounds such as vinyl chloride and the alpha haloethers results in carcinogenesis, possibly related to the fact that these agents or their metabolites are powerful alkylating agents. It seems reasonable that a similar mechanism might apply to the chemically related halogenated anesthetics. Halothane is known to be metabolized, but limited information is available concerning the reactive intermediates which covalently bind to the liver. These or similar molecules are likely to be involved in its potential toxicity and carcinogenicity. The metabolism of nitrous oxide remains to be confirmed. On a theoretical basis its biodegradation to nitrites or nitrosamines would produce mutagenic and carcinogenic effects. Study of the metabolism of these two anesthetics, identification of their reactive intermediary metabolites and determination of their binding properties, will help determine whether anesthetic metabolism is responsible for the observed toxicity. Such information will further guide our search for new and safer anesthetics and help establish standards for the protection of occupationally exposed operating room personnel.