Age and gender have been reported to play a crucial role in modulating the disposition of pharmacological agents, and to influence the activities of cytochrome P450 (CYP) 2D6, a drug-metabolizing enzyme involved in the disposition of clinically used drugs. In the present study, the effects of age and gender on the CYP2D6 activity were evaluated using dextromethorphan as a probe drug in humans. Healthy young (20<age<30years, n=60) and old age (age >60years, n=60) subjects were enrolled and were given 15mg dextromethorphan orally. Blood samples were collected before and 3h after medication. Dextromethorphan and its metabolite dextrorphan were measured using HPLC-fluorescence, and dextromethorphan metabolic ratio (MR, log [dextromethorphan/dextrorphan]) was used to evaluate the CYP2D6 activity. Mean (±SD) dextromethorphan MR was -2.42±0.46 for the young male group, -2.28±0.56 for the young female group, -2.46±0.55 for the older male group and -2.34±0.65 for the old female group. Based on our findings, the effects of age and gender on CYP2D6 activity were not statistically significant. The results of the present study indicate that age and gender play a minor role in the modulation of CYP2D6 activity in the Korean population.