Halothane (approximately G mg/100 ml) administered to isolated rat atria produced about the same degree of contractile depression whether or not glucose was present in the bathing medium. Thus, the depressant action of halothane is independent of exogenous glucose and cannot be simply attributed to a block in glucose uptake or phosphorylation to glucose-G-phosphate. The rate of depression of contractility induced by talothane in the presence of glucose is much faster than that induced when glucose is omitted from the medium, further suggesting that the site of action is not glucose uptake or phosphorylation. The rate of depression induced by halothane is similar to those seen with the known inhibitors of glycolysis, citrate and bicarbonate-free medium. The action probably takes place at the glucose phosphate isomerase step responsible for converting glucose-G-phosphate to fructose-G-phosphate. Previous reports have ruled out actions after this step. The possibility of multiple sites of action cannot be ruled out.