OBJECTIVE: To determine the efficacy and safety of cholestyramine therapy in young children with familial hypercholesterolemia. SUBJECTS: Boys aged 6 to 11 years (n = 57) and girls aged 6 to 10 years (n = 39) with familial hypercholesterolemia. DESIGN: After 1 year of a low-fat, low-cholesterol diet, children with low-density lipoprotein (LDL) cholesterol levels ≥4.9 mmol/L (190 mg/dl) or ≥4.1 mmol/L (160 mg/dl) in the presence of familial premature cardiovascular disease were randomly assigned to a double-blind comparison of 8 gm cholestyramine (n = 36) and placebo (n = 36) for 1 year. OUTCOME MEASURES: The primary efficacy and safety outcomes were serum LDL cholesterol levels and height velocity, respectively. Secondary safety outcomes were erythrocyte folate, total plasma homocysteine, serum fat-soluble vitamins, and side effects. RESULTS: Twenty-two subjects in the cholestyramine group and 26 in the placebo group completed the 1-year study. Most withdrawals from the study were related to unpalatability of the study drug or placebo. The LDL cholesterol levels changed by -16.9% (95% confidence interval, -10.8% to -22.9%) in the cholestyramine group compared with 1.4% (95% confidence interval, -4.4% to 7.2%) in the placebo group. Mean height velocity standard deviation scores during 1 year for the children in the cholestyramine and the placebo groups who had not started puberty were 0.24 ± 1.14 and 0.11 ± 0.68, respectively (not significant). In the cholestyramine group, mean levels of 25-hydroxyvitamin D decreased. One girl had low folate and elevated homocysteine levels, and there was one case of intestinal obstruction caused by adhesions. CONCLUSIONS: Significant reductions in LDL cholesterol are achievable during treatment with cholestyramine in about half of eligible children. Growth is not adversely affected. Folate deficiency may occur, even with a low dose of cholestyramine, and vitamin D supplements should be considered. Caution should possibly be exercised in starting cholestyramine therapy within 3 months of abdominal surgery in children. (J PEDIATR 1996;129:42-9)