1. The effects on oxygen consumption of agents that modify Na(+)-permeability were examined in mouse diaphragm muscle perfused with a bathing solution that contained (+)-tubocurarine in a flow-through mode. Twitch tension and levels of Na+ and K+ in the muscle were also measured. 2. Unstimulated preparations decreased the concentration of oxygen in the bathing solution, indicating a basal level of oxygen consumption. Electrical stimulation of the muscle further decreased the concentration of oxygen. Potassium cyanide eliminated both the basal and the stimulated consumption of oxygen. 3. Veratridine facilitated the effect of stimulation at 0.1 Hz on both the consumption of oxygen and the twitch tension. Ouabain antagonized those effects. 4. Twitch contractions were blocked in the presence of dantrolene sodium or by pretreatment with ethylene glycol. Electrical stimulation of such preparations still caused a residual but considerably decreased consumption of oxygen. Ouabain and tetrodotoxin reduced the residual consumption of oxygen. 5. Ouabain significantly increased the levels of Na+ in the tissue, while veratridine alone did not. The effect of ouabain was further potentiated by the simultaneous presence of veratridine. 6. These results indicate that the enhancement of the sarcolemmal permeability to Na+ increases the rate oxygen consumption. This concept supports the hypothesis that Na+ homeostasis depends on energy consumption.