The green tea gallocatechins, (-)-epigallocatechin-3-O-gallate (EGCG)(IC50 = 0.69 mu M), (-)-gallocatechin-3-O-gallate (GCG)-(IC50 = 0.67 mu M), (-)-epicatechin-3-O-gallate (ECG) (IC50 = 1 3 mu M), and theasinensin A (IC50 = 0.13 mu M), were found to be potent and selective inhibitors of rat squalene epoxidase (SE), a rate-limiting enzyme of cholesterol biogenesis. On the other hand, flavan-3-ols without galloyl group at C-3 did not show significant enzyme inhibition. It was demonstrated for the first time that the cholesterol lowering effect of green tea may be attributed to their potent SE inhibition activities. Inhibition kinetics revealed that EGCG inhibited SE in noncompetitive (K-I = 0.74 mu M), and non-time-dependent manner. The potent enzyme inhibition would be caused by specific binding to the enzyme, and by scavenging reactive oxygen species required for the monooxygenase reaction.