The ability of isolated rat liver milochondria to accumulate calcium in the presence of various concentrations of halothane was studied. Calcium transport into mitochondria is completely prevented by true uncouplers of oxidative phosphorylation. Mitochondrial calcium accumulation continued in the presence of halothane concentratoins as high as 4 per cent. The rate of calcium accumulation showed as halothane levels increased, but the amount accumulated was the same. The conclusion is that halothane is not a true uncoupler of oxidative phosphorylation, and that any uncoupling with anesthetic levels must be very limited. Malignant hyperpyrexia associated with halothane anesthesia is probably not the result of a direct uncoupling of oxidative phosphorylation in normal mitochondria. Greater susceptibility of mitochondria in individuals prone to hyperpyrexia reactions for genetic reasons is not ruled out.