The objective of this study was to evaluate the kinetics of both free and esterified forms of cholesterol contained in a emulsion that binds to LDL receptors (LDE) in subjects with heterozygous familial hypercholesterolemia (FH), and the same subjects under the effects of high-dose simvastatin treatment, as compared with a control normolipidemic group (NL). Twenty-one FH patients (44.0 +/- 13.0 yr, 12 females, LDL cholesterol levels 6.93 +/- 1.60 mmol/L) and 22 normolipidemic patients (44.0 +/- 15.0, 10 females, LDL cholesterol levels 3.15 +/- 0.62 mmol/L) were injected intravenously with 14C-cholesteryl ester and 3H-cholesterol. FH patients were also evaluated after 2 mon of 40 or 80 mg/d simvastatin treatment, and plasma samples were collected over 24 h to determine the residence time (RT, in h) of both LDE labels, expressed as the median (25%; 75%). The RT of both 14C-cholesteryl ester and 3H-cholesterol were greater in FH than in NL [FH: 36.0 (20.5; 1191.0), NL: 17.0 (12.0-62.5), P = 0.015; and FH: 52.0 (30.0; 1515.0); NL 20.5 (14.0-30.0) P < 0.0001]. Treatment reduced LDL cholesterol by 36% (P < 0.0001), RT of 14C-cholesteryl ester by 49% (P = 0.0029 vs. baseline), and 3H-cholesterol RT by 44% (P = 0.019 vs. baseline). After treatment, the RT values of 14C-cholesteryl ester in the FH group approached the NL values (P = 0.58), but the RT of 3H-cholesterol was still greater than those for the NL group (P = 0.01). The removal of LDE cholesteryl esters and free cholesterol was delayed in FH patients. Treatment with a high dose of simvastatin normalized the removal of cholesterol esters but not the removal of free cholesterol.