The pharmacokinetics and body distribution of amiodarone and desethylamiodarone were investigated in rats following a single intravenous dose of 100 mg/kg and 150 mg/kg of amiodarone. The decline in serum and tissue concentrations of amiodarone and desethylamiodarone are described by biexponential functions. All aspects of the typical kinetic profile of the drug and its major metabolite, desethylamiodarone, are discussed. Amiodarone is preferentially distributed in decreasing order in thyroid gland, lung, kidney, liver, heart, adipose tissue, skeletal muscle and brain. The metabolite desethylamiodarone showed a distribution pattern which is similar to that observed for the parent drug. Our study indicates an extensive distribution of amiodarone, with the thyroid gland and lung as organs with specific binding sites or uptake mechanisms and adipose tissue as a depot with a large storage capacity. We also found a very extensive distribution of the metabolite desethylamiodarone with mainly lung and thyroid gland and to some lesser extent kidney, liver and heart as organs with sites of metabolism and/or specific binding sites or uptake mechanisms and fat as a reservoir for the drug. Our data demonstrate the advantages of intravenous loading dosages of amiodarone over oral doses, since considerably higher and longer lasting effective serum and tissue concentrations of amiodarone are reached while lower quantities of the less cardio-active metabolite are formed.