The prediction of pharmacokinetic parameters in humans from data obtained in lower animals can be of considerable importance in the process of drug development. Successful extrapolation will facilitate drug dosing transitions from animals to man and accelerate the drug testing process. Existing literature indicates that for the prediction of pharmacokinetic parameters, data from at least three animal species are used. Some investigators have used only two species to predict clearance and volume in humans. The objective of this paper is to investigate and try to determine if a two species scale-up model is as reliable as a three or more species model. Twelve compounds were chosen randomly from literature and clearance and volume of distribution were scaled-up from two species and compared to predictions obtained from more than two species. The findings in this study indicate that: (1) three or more species are needed for a reliable prediction of clearance; and (2) volume of distribution of a compound is predicted equally well using data from two species or more.