In humans, diets rich in fish oil (containing n-3 FA) decrease the incidence of coronary artery diseases. This is thought to be caused by the induction in liver and skeletal muscle of genes involved in lipid oxidation, and to the repression in liver and adipose tissue of genes responsible for lipogenesis. n-3 FA are known to reduce the synthesis of FA and TG in the liver, resulting in a decrease of plasma concentrations of TG-rich lipoproteins. On the other hand, little is known of a possible effect of n-3 FA on HDL metabolism. To investigate this question, female C57Bl/6J mice were fed an n-3 FA-enriched diet for 16 wk. As expected from previous studies, we found that total cholesterol, TG, and phospholipids were reduced in the plasma of treated mice. We also found that HDL-cholesterol decreased after this treatment and that the in vivo fractional catabolic rate of HDL-cholesteryl ester was significantly higher in treated mice than in control mice fed a standard diet. Consistent with these results, treated mice exhibited increased uptake of HDL-cholesteryl ester in the liver. Moreover, quantitative reverse transcriptase-PCR analysis showed a two- to threefold increase in scavenger receptor B-1 gene expression. Taken together, these results suggest that an n-3 FA-enriched diet stimulates one step in the reverse cholesterol transport in mice, probably by increasing the amount of the scavenger receptor class B-1. These effects of n-3 FA on HDL metabolism may contribute to their beneficial effects on the vasculature.