Alterations in heart and liver metabolism were determined periodically in Sprague-Dawley rats pair-fed a liquid diet (ethanol, 36% of calories) for times as long as 1 year. In liver mitochondria the rate of ATP synthesis was lowered significantly after ethanol administration for 1 month and longer feeding periods. In liver microsomes from ethanol-fed animals, ethanol oxidation and aniline hydroxylation increased 1.5- and 3.5-fold, respectively, after 1 month and remained elevated at the longer feeding intervals. Electron microscopic analyses of heart left ventricles revealed no alterations from ethanol consumption for 1 month. Alterations including disrupted mitochondrial cristae, dilatation of sarcoplasmic reticulum, and widening of the intercalated discs were observed after 6.5-month feeding periods. Myocardial concentrations of creatine, creatine phosphate, ATP, ADP, and Pi remained constant even after ethanol consumption for 9 months. After a 12-month feeding period slight changes in cardiac mitochondrial energy-linked properties were observed which were not as pronounced as those occurring in liver mitochondria. The activity and oligomycin sensitivity of the ATPase were not altered in cardiac mitochondria, whereas in liver preparations significant alterations in these properties of the ATPase were apparent after ethanol consumption for 1 month and the longer feeding periods. These observations suggest that the liver responds more quickly and dramatically to chronic ethanol consumption than does the heart.