The activation of LDL receptors was described recently in a human hepatoma cell line (Hep G2) exposed both to alpha + alpha' subunits from 7S soy globulin and to Croksoy(R)70, a commercial isoflavone-poor soy concentrate. To assess the final identity of the peptide(s) putatively responsible for the biochemical effect, experiments were performed in Hep G2 cells, exposed either to synthetic peptides corresponding to specific sequences of 7S soy globulin or to peptides from the in vitro digestion of Croksoy(R)70. Moreover, the ability of the whole 7S globulin, its subunits and whole Croksoy(R)70 to interfere in the apolipoprotein B (apo B) secretion in the medium as well as in sterol biosynthesis was evaluated in the same model. Increased (125)I-LDL uptake and degradation vs. controls were shown after Hep G2 incubation with a synthetic peptide (10(-)(4) mol/L, MW 2271 Da) corresponding to positions 127-150 of the 7S globulin. Cells exposed to Croksoy(R)70 enzyme digestion products showed a more marked up-regulation of LDL receptors vs. controls, compared with vs. Hep G2 cells incubated with undigested Croksoy(R)70. Among soy-derived products, only the 7S globulin inhibited apo B secretion and (14)C-acetate incorporation when tested in Hep G2 cells at a concentration of 1.0 g/L. These findings support the hypothesis that if one or more peptides can reach the liver after intestinal digestion, they may elicit a cholesterol-lowering effect. Moreover, the protein moiety, devoid of isoflavone components, is likely to be responsible for this major biochemical effect of soy protein.