Fabry's disease is a glycosphingolipid storage disease associated with premature generalized arteriosclerosis. Plasma low density lipoprotein (d 1.019--1.055 g/ml; LDL) was isolated from 4 healthy male volunteers (LDL-N) and from 4 patients with Fabry's disease (LDL-F), in whom plasma globotriaosylceramide (GbOse3) levels were 2--4 times above normal. LDL-N was labeled with 131I and LDL-F with 125I by the iodine monochloride method; both were then injected together intravenously into 4 mongreal dogs. The rates at which they were metabolized were determined by measuring plasma radioiodine levels daily for 7--8 days. No significant difference (Fisher's F-test) was observed between LDL-N and LDL-F in terms of the size of the intravascular compartments (LDL-N, 86.3 +/- 4.2%;; LDL-F, 94.2 +/- 7.7%), biological half-lives (LDL-N, 24.1 +/- 4.2 h; LDL-F, 23.5 +/- 3.7 h), or fractional catabolic rates (LDL-N, 0.849 +/- 0.066; LDL-F, 0.796 +/- 0.070). The results indicate that significant abnormalities of the neutral glycosphingolipid composition of LDL, such as occur in Fabry's disease, do not affect the metabolism of the lipoprotein apoprotein in dogs. The arteriosclerosis in patients with the disease is probably due to damage to vessel walls occurring as a result of defective GbOse3 metabolism and accumulation of glycosphingolipid in the tissue, rather than to abnormal LDL metabolism.