Diltiazem (DTZ) 5 mg/kg was given to rabbits either orally (n = 5) or intravenously (n = 6). Plasma concentrations and urinary excretion of DTZ and its metabolites were determined by a high performance liquid chromatography assay (HPLC) for 12 and 48 h post dose, respectively. The results showed that the metabolism and disposition of DTZ in rabbits was similar to that of humans, mean absolute bioavailability (F) of DTZ was approximately 30% and the systemic clearance was 64.0 ml/min/kg. The metabolism of DTZ between the two routes of administration was quantitatively different in that higher plasma concentrations of the metabolites were observed after the intravenous dose. This could be a result of incomplete oral absorption, higher clearance of DTZ and the metabolites during the first pass through the liver (i.e. higher sequential first pass effect), and/or extrahepatic metabolism. On the basis of the plasma concentration-time profiles and urinary excretion of DTZ and its metabolites, it is concluded that the rabbit is a suitable animal model to investigate the kinetics and metabolism of DTZ.