Background: The wide interindividual differences in the responsie of nortriptyline following conventional dose is well documented. Nortriptyline is mainly metabolized by 10-hydroxylation, which accounts for about 70% of dose recovered in urine as free or conjugated forms. The 10-hydroxylation of nortriptyline is suggested to be catalyzed by debrisoquin 4-hydroxylase(CYP2D6) from the result of in vitro and in vivo studies. Metoprolol is metabolized via CYP2D6 to ${alpha}-hydroxymetoprolol$, and the ratio of metoprolol and ${alpha}-hydroxymetoprolol$ is used as an index of metabolic capacity of CYP2D6. By assessing the correlation between metoprolol metabolic ratio(MR) and nortriptyline clearance, we want to confirm the genetic control mechanism of the major metabolic pathway of nortriptyline in vivo. Method: Fifteen healthy, unrelated, male volunteers participated in the study. They were phenotyped for individual ability to hydroxylate metoprolol before single dose pharmacokinetic study of nortriptyline. Venous blood samples were collected serially after oral administration of a single dose of either 25 or 50mg nortriptyline($Sensival^{circledR}$) and plasma concentration of nortriptyline was measured by HPLC method. Plasma concentration-time data of nortriptylinem was analyzed by non-compartmental method. Results: The mean values of metoprolol MR and nortriptyline clearance of 15 tested subjects were $1.93{pm}2.02$ and $55.37{pm}30.28$ L/hr, respectively. The nortriptyline clearances were well correlated $({gamma}_s=-0.84,;p<0.01)$ with the metoprolol MR values. Conclusion: The correlation between the metoprolol MR values and nortriptyline clearances provides a strong evidence that the hydroxylation of nortriptyline and metoprolol is under the same genetic or cosegregated control.