Homozygous familial hypercholesterolemia is refractory to standard dietary or drug therapy. Recent studies, however, suggest that a high-carbohydrate/low-fat diet may reduce circulation cholesterol levels in normal or hyperlipidemic subjects. In this regard, we treated a nine year old boy with homozygous familial hypercholesterolemia with a liquid formula diet containing 82 to 90 percent of total calories as glucose. The diet was given as a constant nasogastric infusion or as intermittent daytime drinks followed by a nighttime infusion. Plasma total and low-density lipoprotein cholesterol fell from basal levels of 719 mg/dl and 676 mg/dl to 456 mg/dl and 434 mg/dl, respectively, after one week of therapy. After approximately 14 weeks of treatment, plasma total and low-density lipoprotein cholesterol levels were 311 mg/dl and 277 mg/dl, each representing approximately a 58 percent decrease from basal levels. The fall in circulating cholesterol levels was accompanied by a regression of xanthomatous skin lesions, a rise in plasma insulin levels and no change in plasma glucose or glucagon concentrations. No adverse effects of therapy occurred. We conclude that high-carbohydrate diets may be a safe and effective adjunct in the treatment of homozygous familial hypercholesterolemia.