The pharmacokinetics and body distribution of amiodarone and desethylamiodarone were studied in rats after single oral administration of 100 mg/kg and 200 mg/kg of amiodarone. The time-course of the concentrations of the drug and its main metabolite was determined by high performance liquid chromatography in serum and tissues up to 24 h. The mean absorption half-life of amiodarone was 1.83 h for both dosages and the mean elimination half-life was 15 h after the 100 mg/kg dosage and 105 h after the 200 mg/kg dosage. The mean bioavailability of oral amiodarone ranged from 17% to 60% with an average of 39%. Desethylamiodarone, the major metabolite of amiodarone, was present over the 24 h period of observation in relatively low levels of 30 to 60 ng/ml after the 100 mg/kg dose and 50 to 110 ng/ml after the 200 mg/kg dose respectively, which is circa 4% and 7% of the corresponding parent drug level. Amiodarone is preferentially distributed in decreasing order in lung, liver, thyroid gland, kidney, heart, adipose tissue, muscle tissue and brain. The metabolite desethylamiodarone exhibited a distribution pattern comparable to the parent drug. However, its maximum concentrations in serum and tissues were consistently lower than the corresponding amiodarone concentrations and varied from 18 to 55% (mean 27%), depending on the acute oral dose applied and on the kind of tissue. The amiodarone tissue/serum concentration ratios were high in lung tissue (60-100) and moderate to high in the other tissues except brain (3-60), and indicate an extensive distribution of the drug with the lung as an organ with specific binding sites or uptake mechanisms and adipose tissue as a reservoir with a large storage capacity. The metabolite tissue/serum concentration ratios were very high in lung tissue (500-800), high in renal, thyroid, liver and adipose tissue (80-200) and moderate in the other tissues except for brain (20-60); they indicate a very extensive distribution of desethylamiodarone with, primarily, lung and to some lesser extent kidney, liver and thyroid gland as organs with sites of metabolism and/or specific binding sites or uptake mechanisms and fat as a reservoir for the drug. A marked increase in the accumulation of amiodarone and desethylamiodarone was observed in adipose tissue after chronic oral administration, whereas the rise in kidney and brain was less pronounced and in the remaining tissues it was insignificant. Our data suggest that the rat is a good model for describing the single oral dose pharmacokinetics and body distribution of amiodarone and desethylamiodarone in man.