The authors studied the effects of substituting deuterium for hydrogen in several volatile anesthetics on their metabolism in the Fischer rat. Substitution of deuterium in the ethyl portion of methoxyflurane increased the metabolic production of fluoride ion by 19 per cent when administered at a concentration of 0.05 per cent. Total replacement of hydrogen by deuterium resulted in a 29 per cent decrease in the amount of fluoride produced, while deuteration of only the methoxyl group produced a 33 per cent decrease in fluoride produced. Deuteration of halothane resulted in a 15 or 26 per cent decrease in serum bromide at 0.75 per cent or 1.0 per cent, respectively. Deuteration in the ethyl portions of enflurane and two experimental agents, CF2HOCF2CFBrH and CF2HOCF2CCl2H resulted in 65, 76, and 29 per cent decreases in urinary fluoride, respectively. Anesthesia with deuterated chloroform at a concentration of 0.36 per cent produced a 35 per cent decrease in serum glutamic pyruvic transaminase (SGPT). It is concluded that deuteration of volatile anesthetics changes their metabolism, in most cases producing decreases in metabolism. This effect may lessen the organ toxicity believed to occur with some of these anesthetics.