A 30 mg kg-1 intravenous bolus of 14C-amiodarone (19 microCi kg-1) was given to male Sprague-Dawley rats pretreated with 0 (vehicle), 25 or 100 mg kg-1 day-1 of amiodarone HCl orally for 37-42 days to determine the effects of dose and duration of administration on the disposition kinetics of amiodarone. Serial blood samples and total urine were collected over 48 hours and assayed for 14C-amiodarone by liquid scintillation counting following separation by HPLC. In all three groups, the blood 14C-amiodarone concentration-time curves declined bioexponentially with terminal half-lives (t1/2 beta) ranging from 14-22 hours. No differences in beta, t1/2 beta, or central compartment volume (Vc) were observed between the three groups of rats. In the rats pretreated with 100 mg kg-1 day-1 of amiodarone HCl for 5-6 weeks, amiodarone clearance (CL) and steady state volume of distribution (Vss) were reduced 52 per cent (12.2 to 5.9 ml min-1 kg-1) and 41 per cent (11.73 to 6.97 l kg-1), respectively. At the lower amiodarone daily dose, no changes in CL or Vss were observed. Negligible levels of radioactivity were detected in the urine. Amiodarone accounted for approximately 30-40 per cent of the total radioactivity in each blood specimen. This study demonstrated that CL and Vss were dose-dependent, and that beta, t1/2 beta and Vc were dose-independent. The results further suggested that the disposition kinetics of amiodarone were independent of the duration of drug administration.