Brain mitochondria isolated from rats following 10 weeks of chronic exposure to ethanol were not deficient in respiratory function or in rates of calcium uptake under control conditions. Ethanol (80 mM) in the incubation medium caused significant depression in the respiratory and ATP-dependent rates of calcium uptake in control mitochondria, but did not affect mitochondria from ethanol-tolerant rats. Chronic exposure to ethanol causes mitochondria to take calcium up at a normal rate when challenged acutely by ethanol.