Apolipoprotein B-48 (ApoB-48) is a constituent of chylomicrons and chylomicron remnants, and is thought to be one of the risk factors for atherosclerosis. We evaluated the effect of L-thyroxine (L-T(4)) replacement on serum ApoB-48 levels in patients with primary hypothyroidism. Eighteen patients with overt hypothyroidism (OH) and 18 patients with subclinical hypothyroidism (SH) participated in the study. The lipid profiles, including ApoB-48, were measured in patients with hypothyroidism before and 3 months after L-T(4) replacement. After L-T(4) replacement, the serum concentrations of all lipoproteins, exclusive of lipoprotein(a) (Lp(a)), were significantly decreased in patients with OH. In patents with SH, the serum levels of total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C), remnant-like particle cholesterol (RLP-C), apolipoprotein B (ApoB), and ApoB-48 decreased significantly after L-T(4) replacement. The serum levels of triglycerides (TG), HDL-C, low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA-1), and Lp(a) did not change significantly. In all 36 patients, the reduction in the ApoB-48 levels correlated significantly with the reduction in TSH levels (r = 0.39, P<0.05). This study showed clearly that L-T(4) replacement might reduce serum levels of ApoB-48 in both OH and SH patients. Such altered serum levels of ApoB-48 in patients with OH and SH may be related to the disturbed metabolism of chylomicron remnants in patients with hypothyroidism.