The ability of alcohol extract of isolated soy protein to contribute to the hypochoesterolemic effect mediated by the intake of soy protein was tested in gerbils. Gerbils were assigned to five different groups (n = 8) and provided experimental diets for 28 d. Diets contained either casein or alcohol-washed isolated soy protein (ISP). The ISP diet was provided alone, or supplemented with one of three different levels of an alcohol extract of isolated soy protein contributing either 2.1, 3.6 or 6.2 mg isoflavones/g protein. Gerbils fed all of the soy-based diets had significantly lower (P < 0.05) total cholesterol, LDL + VLDL cholesterol, and apolipoprotein B concentrations than those fed casein. The addition of the alcohol extract to ISP did not reduce serum cholesterol concentrations any further, but reduced hepatic apolipoprotein A-I mRNA levels (P < 0. 05) compared with casein- and ISP-fed groups. Levels of apolipoprotein E mRNA were not affected by diet. These data suggest that in gerbils, consumption of an isoflavone-containing extract does not contribute to the hypocholesterolemic effect of alcohol-extracted soy, but may influence lipid metabolism by altering gene expression for lipid-related genes.