Objective: To relate clinical factors to the development of cardiovascular atherosclerosis for patients with homozygous familial hypercholesterolemia. Background: Homozygous familial hypercholesterolemia is associated with extreme elevations in levels of cholesterol causing aggressive atherosclerosis. Methods: We reviewed 10 children, 8 of whom were male, assessed at a single institution. We found that individual characteristics, levels of lipid, cardiovascular investigations, and management were related to the activity of low density lipoprotein receptors. Results: Activity of low density lipoprotein receptors was defined as absent, being less than 2% of normal, in 4 patients who presented at the ages of 0.3, 1.4, 1.8, and 4.5 years, respectively. The activity was minimal, representing 5%–30% of normal, in another 4 patients presenting at the ages of 6.1, 9.6, 9.9, and 12 years, and was undetermined in 2 patients who presented at the ages of 3.5, and 12.1 years. Levels of low density lipoprotein cholesterol at presentation ranged from 12.2 to 24 millimoles per litre. Plasmapheresis was performed bi-weekly in 9 patients. Patients with absence of receptor activity were less likely to have a serial decrease in the levels of low density lipoprotein cholesterol prior to plasmapheresis, and one of these patients was increased to weekly plasmapheresis. In addition, they had more aggressive cardiovascular involvement of the coronary arteries, aortic valve and aorta, requiring surgical intervention at the age of 8 and 12 years in 2 patients, with sudden death at the age of 3.1 years in one patient. In contrast, 1 patient with minimal receptor activity had surgical intervention at the age of 16.6 years and another patient died suddenly at the age of 33.6 years. Conclusion: Complete cardiac assessment is recommended at presentation. The frequency of plasmapheresis should be adjusted according to the activity of low density lipoprotein receptors and the individual response of the patient.