In animal the plasma cholesterol-lowering activity of 2,4,6-trihydroxyacetophenone (THA) is due to enhanced cholesterol 7alpha-hydroxylase (CYP7A1) activity. We have examined the effect of THA on CYP7A1 activity and mRNA level in HepG2 cells. THA stimulated CYP7A1 activity in a concentration- and time-dependent manner. After exposure for 24 h, 1 muM THA induced CYP7A1 activity 160+/-8% and mRNA level 166+/-21% (mean+/-S.E.M.) of control. Moreover THA antagonized the inhibitory regulation of chenodeoxycholic acid on CYP7A1 mRNA expression. These results indicated that THA increases CYP7A1 activity in human HepG2 cells by stimulating mRNA transcription.