SummaryThree patients with Menkes' disease, an inherited disorder of copper transport, were studied to determine whether the copper deficiency was associated with a lipoprotein disorder. Hypocuprinemia was documented in all three cases. Two patients had severe copper and ceruloplasmin deficiencies, whereas the third patient had a less severe deficiency. Hypertriglyceridemia was observed in the first patient, and elevations in triglyceride, cholesterol, apolipoprotein B (ApoB), and apolipoprotein C-III (ApoC-III) occurred predominantly in the very low density lipoprotein fraction (VLDL). This patient had normal lipoprotein lipase activity but mild glucose intolerance. The second patient had a borderline high cholesterol level with normal plasma triglycerides and apolipoproteins, whereas the third patient appeared to have normal total cholesterol but slightly higher triglycerides with elevated plasma apolipoprotein E (ApoE). No striking differences were observed in the chemical composition of all lipoprotein subfractions between patients and controls except that the neutral lipid content of VLDL was higher in patients than in controls. The ApoB was initially normal in molecular weight but degraded faster than the controls during storage. The appearance of the major low density lipoprotein (LDL) fraction of the first two patients was opaque white, in contrast to clear yellow in the third patient and in the age- and diet-matched controls. This abnormal appearance of LDL in these patients was associated with low plasma levels ofβ-carotene and ceruloplasmin. These findings suggest that decreased serum copper levels may be associated with lipid and lipoprotein abnormalities and may enhance lipid peroxidation of LDL accounting for the color change. The increase in neutral lipids and the damaging effects on lipoprotein-transported substances may lead to atherosclerosis.