The effect of thyroid hormones on concentrations of lipoprotein(a) [Lp(a)] was analyzed in 60 patients with active thyroid dysfunction (hyperthyroidism 30 cases, hypothyroidism 32 cases, and 2 cases with opposite changes) and after normalization of the thyroid state. Treatment of hyperthyroidism increased the mean Lp(a) concentrations by 60% (from 73 to 102 mg/L, P < 0.002); at the same time, low-density lipoprotein cholesterol (LDL-C) increased by 53% (from 2.6 to 3.7 mmol/L, P < 0.0001) and apolipoprotein B (apo B) by 35% (from 0.91 to 1.17 g/L, P < 0.0005). In hypothyroidism, the opposite changes were observed: mean Lp(a) decreased from 136 to 114 mg/L (10%, P < 0.02), LDL-C from 4.6 to 3.9 mmol/L (13%, P < 0.01), and apo B from 1.51 to 1.20 g/L (14%, P < 0.01). Although the changes in Lp(a) concentrations did correlate with changes of LDL-C during treatment of hyperthyroidism (r = 0.43, P < 0.05), and with changes in apo B during thyroxine-substitution therapy for hypothyroidism (r = 0.46, P < 0.05), we observed no associations between Lp(a) and LDL-C or apo B in the euthyroid state. These data cannot rule out the possibility that the thyroid hormone-induced increase in LDL-C receptor activity was responsible for the decreased concentrations of Lp(a) in hyperthyroidism. Given that LDL-C is approximately 30% of the Lp(a) molecule but the changes in Lp(a) concentrations are comparable with those in LDL-C (60% vs 53%), and given that Lp(a) is metabolized by an LDL-C-receptor-independent pathway, the present data suggest a direct effect of thyroid hormones on Lp(a) synthesis.