The physiological activities of some phenolic compounds affecting hepatic fatty acid synthesis in mice were compared. Male ICR mice were fed an experimental diet containing 1% quercetin dihydrate, rutin, or ferulic acid or a control diet free of phenolic compounds for 15 days. Quercetin significantly lowered serum cholesterol and phospholipid levels in mice. Also, the serum triacylglycerol level was considerably lower in mice fed the quercetin-containing diet than in those fed a diet free of phenolic compounds, although the difference was not significant. Rutin and ferulic acid did not affect these parameters. Quercetin significantly reduced the activity and mRNA levels of various enzymes involved in hepatic fatty acid synthesis. Rutin reduced a few of the parameters for lipogenesis, but ferulic acid did not affect any of the parameters. It was suggested that a reduction in hepatic lipogenesis is the mechanism underlying the hypolipidemic effect of quercetin.