1. The lipid and protein composition of subfractions of plasma low-density lipoprotein (LDL) has been determined in nine patients with primary hypothyroidism before and after 3 months of thyroxine therapy. Analyses were also made of subfractions of very-low-density lipoprotein (VLDL) in four of the patients.

2. Before therapy seven of the patients had elevated LDL-cholesterol and two had increased VLDL-cholesterol concentrations. On thyroxine replacement the mean LDL-cholesterol fell to normal. No significant change occurred in the concentration of cholesterol in VLDL or in high-density lipoprotein (HDL).

3. The concentrations of cholesterol, triglyceride and apolipoprotein B (apoB) were increased in the LDL subfraction of Sf 10·4–20, which corresponds mainly to intermediate-density lipoprotein. This subfraction showed a marked fall on therapy. The cholesterol and apoB concentrations in the major LDL fraction of Sf 5·7–12 also decreased on therapy, but the fall in the subfraction of Sf 3·5–6·5 did not reach statistical significance.

4. Only the VLDL subfraction of smallest size (Sf 20–60) had any abnormality before therapy, with an increased concentration of cholesterol. On thyroxine the concentration of triglyceride rose in the VLDL subfractions.

5. These data suggest that thyroxine exerts its major effect on lipoprotein metabolism by promoting the conversion into LDL of intermediate-density lipoprotein, formed by catabolism of VLDL.

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