The effect on serum lipid and lipoprotein levels of a standard low fat, low cholesterol diet was compared with that of a soy protein-substituted low fat, low cholesterol diet in 23 children with familial or polygenic hypercholesterolemia: 12 boys and 11 girls (mean age, 9.3 +/- 4.5 years) were included in this outpatient program. Group 1 received the soy protein diet for 8 weeks; group 2 received the low fat, low cholesterol diet. After an interruption of 8 weeks, each group was placed on the alternate regimen. Fasting blood samples were collected at the beginning of each dietary period. During the soy protein diet, the levels of total cholesterol decreased by 16% in group 1 and 18% in group 2, and low-density lipoprotein cholesterol (LDL-C) levels decreased about 22% in group 1 and 25% in group 2. During the standard low fat, low cholesterol diet, total cholesterol and LDL-C levels were reduced by 8% and 7% in group 1 and by 12% and 13%, respectively, in group 2. The effect on LDL-C was significantly greater (p < 0.05) in the soy protein group than in the low fat, low cholesterol group. We conclude that a diet substituting soy protein for animal protein has a more beneficial short-term effect on total cholesterol and LDL-C levels in children with hypercholesterolemia than a standard low fat diet.