Seventeen patients with heterozygous familial hypercholesterolemia were sequentially treated with: a low cholesterol, fat restricted diet; diet and probucol (500 mg/day); and diet, probucol and niceritrol (1500 mg/day). Concentrations of plasma cholesterol decreased from 348 + 49 mg/dl on diet alone to 304 + 32 mg/dl, to 256 + 30 mg/dl on diet and probucol, and fell to 212 + 41 mg/dl on the combined regimen with niceritrol. Concentrations of LDL-cholesterol declined 13% on diet, and 26% on diet and probucol; the subsequent addition of niceritrol resulted in a 42% fall from the baseline. Plasma concentrations of apolipoprotein B fell 37% on the combined regimen with niceritrol. As a result, normal levels of cholesterol (less than 230 mg) were achieved in thirteen subjects treated with this new combination therapy. Moreover, atherogenic index improved with the addition of niceritrol. These results suggest even a small dose of niceritrol affords opportunity to maintain normal lipid profile in heterozygous familial hypercholesterolemia when given in combination with probucol.