Epimedium koreanum is popular herbal medicine in Korea. Our previous in vitro study has showed that epimedium has a marked inhibitory potential on the activity of cytochrome P450(CYP) isoforms, CYP1A2, 2C19, 2D6, and 3A. The effect of epimedium on CYP activity in vivo was assessed using the cooperstown cocktail regimen. Eight healthy male subjects received cocktail regimen including caffeine, omeprazole, dextromethorphan, and iv midazolam to determine the baseline activities before herbal supplementation(day1). After a week, dried water extract of epimedium was administered for 7days. The cocktail study was conducted on day 8 with first coadministration of epimedium and did again on day 15 after completion of herbal supplementation. Blood samples were drawn serially upto 12 hrs and urine was collected upto 24 hrs after dosing. Midazolam clearance, caffeine (paraxanthine/caffine AUCinf) and omeprazole (OH-omeprazole/omeprazole AUCinf) metabolic ratio were not significantly different from baseline. The urinary Log(dextromethorphan/dextrophan) ratio after epimedium supplementation for 7 days was significantly decreased from baseline. First coadministration of epimedium did not show to have an effect on any CYPs metabolic ratio. This result indicates that long-term treatment of epimedium may induce the CYP2D6 enzyme activity in vivo. However, the in vivo activity of other CYPs was found to be not appreciably influenced by epimedium administration despite its in vitro inhibitory potential. Clinical Pharmacology & Therapeutics (2005) 77, P85–P85; doi: 10.1016/j.clpt.2004.12.217