The lipid-lowering effect of a soy-based protein supplement was evaluated in an 8-week randomized, placebo-controlled trial in patients with hypercholesterolemia. A total of 117 patients (63 men and 54 women) received soy protein, either 15 or 25 g/d or placebo. In the active treatment groups low-density lipoprotein cholesterol levels decreased significantly by 5.9% and 1.1% respectively, but increased by 3.6% with placebo. Total serum cholesterol and apolipoprotein B levels changed significantly in a similar manner. High-density lipoprotein cholesterol, triglycerides, homocysteine, folic acid, and vitamin B12 levels did not change significantly compared with baseline in any of the study groups. All preparations were well tolerated. Soy protein 25 g/d was twice as effective as 15 g/d. In conclusion, soy protein supplementation may effectively reduce serum cholesterol levels and therefore is likely to diminish the risk for cardiovascular disease.