The effect of L-thyroxine therapy on lipoprotein fractions was assessed in 15 patients with overt hypothyroidism (14 women and one man aged 45 +/- 3.9 years; thyrotropin [TSH]: mean +/- SEM, 42 +/- 6.5 mIU/L; range, 20.5 to 106.5) and 14 patients with subclinical hypothyroidism (13 women and one man aged 41 +/- 4 years; TSH: mean +/- SEM, 9.1 +/- 1 mIU/L ; range 5.1 to 17.3). Fasting serum lipid levels were measured initially and 4 months after achievement of a euthyroid state with incremental L-thyroxine therapy (TSH: mean +/- SEM, 1.8 +/- 0.4 mIU/L; range, 0.3 to 4.9 for both groups). In the overtly hypothyroid group, restoration of a euthyroid state was associated with a significant reduction in total cholesterol, and apo B. In the subclinically hypothyroid group, there was a significant reduction of only total cholesterol (199.6 +/- 13.2 v 183.4 +/- 11.6 mg/dL) and LDL-C (13.6 +/- 8.4 v 114 +/- 9.25 mg/dL). In contrast, lipoprotein(a) [Lp(a)] was unaffected by the incremental adjustment of L-thyroxine therapy in both groups (overt, 34.3 +/- 8.8 v 35.6 +/- 6.7 mg/dL; subclinical, 23.0 +/- 8.6 v 29.4 +/- 9.5 mg/dL). We conclude that restoration of a euthyroid state in patients with overt hypothyroidism has no significant effect on Lp(a) levels, and confirm that subclinical hypothyroidism is associated with a significant increase in LDL-C, known to have an atherogenic effect.