The use of herbal supplements has increased dramatically, making drug interactions with these supplements a major concern. Because herbal supplements are not subject to the same regulations as prescription drugs, we hypothesize that the content of their active ingredients may vary among manufacturers, potentially causing a large variation in therapeutic outcome. The present study aimed to test this hypothesis on commonly used herbal products, i.e. black cohosh (BC), grape seed extract (GSE), green tea extract (GTE) and ginseng. Activity of human CYP3A4 enzyme was used as a parameter to determine the effect of these selected herbal supplements from various manufacturers. The contents of an herbal product, equivalent to one capsule, was extracted with methanol. Aliquots of the extract were tested for their ability to inhibit the metabolism of the human CYP3A4 probe quinine, using an in vitro liver microsomal technique. Human liver microsomes and quinine were incubated at 37 degrees C with or without (i.e. control) herbal extract. Formation of quinine's metabolite 3-hydroxyquinine, generated by the CYP3A4-mediated reaction, was measured by HPLC. Seven products of BC were tested, and inhibition of CYP3A4 was not observed. Four brands of GSE had no effect, while another five produced mild to moderate but variable inhibition of CYP3A4, ranging from 6.4% by Country Life GSE to 26.8% by Loma Linda Market brand. Among the supplements tested, GTE produced the most pronounced inhibition of CYP3A4, which ranged from 5.6% by Nature's Resource to 89.9% by Natrol GTE product. Nine ginseng products studied had little to no effect on the activity of CYP3A4. This study suggests that GTE use may cause significant interactions with drugs metabolized by CYP3A4. However, the effect on CYP3A4 varied among different brands of GTE, possibly due to variations in their content of the herbal product's active ingredients.