The present study was designed: (1) to investigate the effects of the inducing agents phenobarbital (PB), 3-methyl cholanthrene (3-MC), and rifampicin (RFP) on paraoxonase (POX) and arylesterase (ARE) in liver and plasma, using the rat as model; and (2) to determine whether the response of both esterase activities to inducers is similar each one or, on the contrary, they are different enzymes. If the former is true, the hypothesis of a unique enzyme instead two different enzymes would become more consistent.Groups of 5 rats were pre-treated with the inducers according to standard protocols. Control rats were either untreated or administered appropriate volumes of vehicle. After killing, liver microsomes were prepared by differential centrifugation and POX and ARE activities as well as protein content were assayed. PB and 3-MC each increased the POX activity in microsomal fraction (58 and 36%, respectively) and ARE activity (61 and 13%, respectively). In addition, only 3-MC was able to increase the esterases activities in plasma (23% POX and 16% ARE). By contrast, RFP decreased both enzyme activities in liver and plasma. Microsomal fraction proteins did not show significative differences between controls and different inducers. Our results indicate that classical enzyme-inducing agents exert divergent effects on POX and ARE in rat plasma and liver microsomes, and support the previous evidence on the identity between the two esterase activities.