The objective of this study was to evaluate whether the predicted clearance of a drug in humans from in vitro human liver microsomes was comparable with the predicted clearance in humans obtained by allometric scaling. Sixteen drugs were randomly selected from the literature and their hepatic clearances were predicted using human liver microsomes. For allometric scaling at least three animal species were used and three methods were utilized to generate allometric equations to predict the clearance in humans: (i) clearance vs body weight (simple allometry); (ii) product of the clearance and maximum life-span potential (MLP) vs body weight; and (iii) the product of clearance and brain weight vs body weight. The choice of one of the methods was based on the 'rule of exponents' as described by Mahmood and Balian /2,3/. The results of this study indicated that the use of human liver microsomes to predict hepatic clearance in humans may not provide reliable predictions. On the other hand, the prediction of clearance in humans using allometric scaling combined with the 'rule of exponents' can provide comparatively better prediction of clearance in humans.