The antiadrenergic actions of amiodarone (Am) are well known but its effect and that of its metabolite, desethylamiodarone (DAm), on β-receptor density (B max) and affinity (K D) are poorly defined. Thus, the acute and chronic effects of Am and DAm on myocardial β-receptors in rabbits were determined relative to changes in thyroid hormones and serum and tissue drug concentrations. B max and K D were measured by radio-ligand binding, thyroid hormones by RIA. and drug levels by HPLC. Compared with controls, intravenous Am (20 mg/kg) reduced B max by 23%(p< 0.05) and DAm (20 mg/kg) by 32%(p< 0.05). After 3 weeks of chronic drug, the corresponding value for Am was 24%(p< 0.05) versus 45%(p< 0.05) for DAm. The effect of DAm was significantly greater (p< 0.05) than that of Am, being comparable to that of Am (− 44%) after 6 weeks. In the case of Am, doubling the dose (and myocardial level) led to no further decrease in B max DAm also reduced B max more following chronic treatment than after acute administration (− 45 versus− 32%), a difference of borderline significance. Following 3 weeks of po Am, T 3 decreased 3%(NS) and reverse T 3 (rT 3) increased 90%(p< 0.05); after 6 weeks, the corresponding values were 25%(p< 0.05) and 181%(p< 0.01). After 1 week of po DAm, T 3 did not change but rT 3 increased by 34%(p< 0.05); after 3 weeks the corresponding values were 21%(p< 0.01) and 64%(p< 0.01). Neither compound affected serum T 4 levels. Thus, Am and DAm reduce B max acutely with a trend for further reduction after chronic therapy as a function of time but not of serum and myocardial drug levels.