Fourteen patients with familial hypercholesterolaemia were managed with dietary advice and simvastatin for 12 months. Either nicotinic acid or cholestyramine resin was added to the regimen if serum cholesterol was not less than 5.5 mmol/l within 18 weeks. After dietary advice but before commencing pharmacotherapy for hyperlipidaemia, arterial stiffness was measured in the common carotid and common femoral arteries. These studies were repeated after 12 months on pharmacotherapy. The primary objective of this study was to determine whether arterial stiffness could be altered with total cholesterol and low density lipoprotein (LDL) cholesterol lowering. Over the 12 month interval, serum total cholesterol, LDL cholesterol and triglycerides fell significantly, whereas high density lipoprotein (HDL) cholesterol and body mass index (BMI) rose significantly. Mean supine blood pressure did not change significantly. Arterial stiffness in the common carotid artery decreased from 1.04 +/- 0.21 x 10(5) N/m2 to 0.63 +/- 0.06 x 10(5) N/m2 (T = -2.67, P < 0.01) over the interval. Stiffness of the common femoral artery decreased from 2.10 +/- 0.57 x 10(5) N/m2 to 0.83 +/- 0.15 x 10(5) N/m2 (T = -2.73, P < 0.01). The change in arterial stiffness was not directly related to changes in circulating lipids or supine blood pressure. Increase in BMI, however, correlated with change in arterial stiffness in the common femoral artery (Rs = 0.53, P < 0.05) but not in the common carotid artery. An increase in BMI was associated with a smaller decrease in common femoral arterial stiffness. Aggressive hypolipidaemic therapy was therefore associated with a favourable effect on arterial wall stiffness.(ABSTRACT TRUNCATED AT 250 WORDS)