The fractional catabolic rate (FCR) for low density lipoprotein (LDL) apolipoprotein B (apo B) was studied to explore the variations in apo B as a possible cause of hypercholesterolemia. The FCR of radioiodine labelled autologous LDL and homologous LDL isolated from a normocholesterolemic subject were compared in forty-nine type II hypercholesterolemic males and females with the mean plasma concentration of total cholesterol of 7.78 mmol/l, LDL-cholesterol 5.41 mmol/l and triglycerides 2.09 mmol/l. In most patients the autologous LDL was catabolized at an equal rate and sometimes even faster than the homologous LDL. However, twelve out of forty-nine patients catabolized homologous LDL 0.8-19.3% faster than autologous LDL and several apo B polymorphisms were determined. No apo B-3500 or apo B-3531 mutations were detected. Patients with XbaI -/- (absence of cutting site) had lower total, IDL and LDL cholesterol and LDL apoB than the other genotypes. Patients with EcoRI +/+ (presence of cutting site) had higher total, VLDL and LDL cholesterol and slower FCR for autologous LDL, and their VLDL was richer in cholesterol than that of patients with the EcoRI +/-. The MspI and ins/del polymorphisms were not associated with variations in the measured parameters. The apo E 4 was associated with higher VLDL and IDL cholesterol, higher triglycerides and LDL apo B than E 3/3. Overall, the determined apo B polymorphisms were not related to the slow clearance of autologous LDL among the 12 patients, in whom autologous LDL was cleared at a slower rate than homologous LDL. In conclusion, hypercholesterolemia can be due to particle-related slow clearance of LDL in some patients. However, this is not a common cause of hypercholesterolemia.