The elimination of felodipine in liver microsomes from dog and man were characterized by Km and Vmax. The results were compared with previous data reported for rat. In all species studied, felodipine was primarily metabolized to its corresponding pyridine analogue. The elimination rate order was rat greater than dog greater than man. The same species difference was observed in vivo for the oral plasma clearance which was; rat 26 1/hr/kg, dog 7.5 1/hr/kg and man 4.3 1/hr/kg. The intrinsic hepatic clearance of felodipine was predicted in vitro from Vmax over Km. The in vitro values were not significantly different from those observed in vivo. Felodipine is a high-clearance drug and the in vivo extraction ratios were about the same in all species: rat 0.80, dog 0.83 and man 0.84. The extraction ratios predicted from the in vitro studies, rat 0.91, dog 0.70 and man 0.80, agreed well with those observed in vivo.