For centuries the South Pacific islanders have consumed kava (Piper methysticum) as a ceremonial intoxicating beverage. More recently, caplets of kava extracts have been commercialized for their anxiolytic and antidepressant activities. Several cases of hepatotoxicity have been reported following consumption of the commercial preparation whereas no serious health effects had been documented for the traditional beverage. A detailed comparison of commercial kava extracts (prepared in acetone, ethanol or methanol) and traditional kava (aqueous) reveals significant differences in the ratio of the major kavalactones. To show that these variations could lead to differences in biological activity, the extracts were compared for their inhibition of the major drug metabolizing P450 enzymes. In all cases (CYP3A4, CYP1A2, CYP2C9, and CYP2C19), the inhibition was more pronounced for the commercial preparation. Our results suggest that the variations in health effects reported for the kava extracts may result from the different preparation protocols used.