Plasma concentrations of total and low-density lipoprotein cholesterol are increased twofold to threefold in patients with heterozygous familial hypercholesterolemia. This sustained increase leads to accelerated rates of cholesterol deposition in the coronary arteries and to the development of tendon xanthomas. To assess whether hypolipidemic therapy with lovastatin, alone and in combination therapy with colestipol hydrochloride or nicotinic acid, results in regression of lipid deposits in the tendons of these patients, we have measured Achilles tendon diameters by xeroradiography before and after treatment. In 20 patients treated for a mean of 43 months (during which time plasma cholesterol concentrations decreased from 430 to 247 mg/dL), the diameter of both the left and right Achilles tendons measured at three different locations decreased by 0.55 to 1.5 mm. Larger reductions were seen in the tendons of seven of these patients who were treated for a mean of 64 months and whose mean concentrations of cholesterol fell from 488 to 279 mg/dL. We conclude that effective long-term hypolipidemic therapy leads to diminution in the size of Achilles tendon xanthomas in patients with heterozygous familial hypercholesterolemia and that such therapy is associated with mobilization of tissue stores of cholesterol in these patients.