The purpose of this experiment was to determine whether halothane interferes with the utilization of lipid as a source of fuel for the contractile process by the isolated rat atria. Rats were starved 24 hours in order to increase the lipid content of the heart. Atria from starved rats were better able to maintain their contractility in the absence of exogenous substrate and also were more resistant to depression by halothane than atria from fed rats. Approximately 11 mg/100 ml (1.41 vol per cent) halothane were necessary to achieve 50 per cent depression of the force of contraction of atria from starved rats whether glucose was present in the bathing medium or not. To achieve the same degree of depression in the presence or absence of glucose in atria from fed rats required about 6.5 mg/100 ml (0.83 vol per cent). Atria from starved rats behaved like atria from fed rats in that the depressant action of halothane was independent of external glucose. The site of action of halothane in either case cannot be related to the uptake or phosphorylation of glucose, but may involve the glucose phosphate isomerase step, as previously suggested. The greater halothane requirement for atria from starved rats suggests that endogenous lipid accumulates during starvation and is used as an energy source for the contractile process in the face of a halothane-induced block in glycolysis. Other possible reasons for the resistance of atria from starved rats to halothane's depressant action are discussed.