Activation of low-density lipoprotein (LDL) receptors has been decribed in a human hepatoma cell line (Hep G2) exposed to the 7S globulin from soy (Lovati et al. J. Agric. Food Chem. 1998, 46, 2474-2480). This in vitro model supports a direct activity of say protein component(s) in lowering LDL cholesterolemia. To ascertain whether alpha or alpha' subunits from 7S globulin, or both, are responsible for the biochemical effect, a mutant soy cultivar, devoid of the alpha' subunit (Keburi), was evaluated in the same model. A commercial isoflavone-poor, heat-hydrolyzed soy preparation found effective in human hypercholesterolemia (Croksoy) was also tested. While Croksoy proved to have a similar activity as the whole 7S globulin, the alpha'-free Keburi variant showed no effect on LDL receptor activation. These findings support the reliability of the human liver cell model in predicting a human hypocholesterolemic activity and suggest that specific peptide!s! may be responsible. Furthermore, they indicate that some say cultivars may be best suited for the preparation of products for human nutritional purposes.