An excess of thyroid hormone is known to produce cardiac dysfunction and failure, i.e., thyrotoxic heart. We studied the protective effect of coenzyme Q10 (CoQ10) on the thyrotoxic heart in 29 rabbits. A group treated with 1-thyroxine sodium salt (T4; 167 micrograms/kg) for 3 weeks showed marked decreases in the myocardial content of norepinephrine (NE) and ATP (0.5 +/- 0.2 microgram/g wet weight, P less than 0.05 and 31.1 +/- 2.6 nmol/mg protein, P less than 0.05, respectively) as compared with a group treated with CoQ10 solvent (2 ml/kg) for 3 weeks (1.1 +/- 0.1 microgram/g wet weight and 45.7 +/- 4.7 nmol/mg protein). The mitochondrial Ca2+ content of the T4 group showed significant increases (21.3 +/- 0.6 nmol/mg protein, P less than 0.05) compared with the solvent group (18.2 +/- 0.8 nmol/mg protein), while the total tissue Ca2+ content of the T4 group was unchanged compared with the solvent group. These biochemical derangements suggest that T4-treated rabbits were in a state of cardiac dysfunction. In contrast, a group which was assigned to concomitant treatment of T4 and CoQ10 (5 mg/kg) for 3 weeks showed no reductions in NE and ATP (0.9 +/- 0.2 micrograms/g wet weight and 44.6 +/- 1.9 nmol/mg protein, respectively) and protected an increase in the mitochondrial Ca2+ content (18.2 +/- 1.2 nmol/mg protein). A group treated with CoQ10 (5 mg/kg) for 3 weeks showed no changes in myocardial NE, ATP, and Ca2+ content in the mitochondria. These results suggest that exogenously administered CoQ10 may protect against biochemical derangements in the thyrotoxic heart.