Subclinical hypothyroidism is a frequent disorder in populations and has been shown to be a risk factor for coronary heart disease (CHD). Less is known about the contribution of lipoprotein (a) [Lp(a)] to the development of CHD in this disorder. Therefore this study was designed to evaluate Lp(a) and other lipoprotein concentrations before and after L-T4 therapy in 20 patients with subclinical hypothyroidism and 20 normal healthy subjects matched for sex, age and BMI. In the basal state of subclinical hypothyroidism, a significant increase in total cholesterol, LDL-cholesterol and apolipoprotein (apo) B concentrations was observed in patients compared with those in the control group. The mean Lp(a) concentration before treatment was 163 +/- 15 mg/L. This is slightly but not significantly higher than those in the control group (131 +/- 15 mg/L). Treatment of subclinical hypothyroidism with a low dose of L-T4 (25 micrograms daily) for 3 months after restoration of euthyroidism led to decreases in levels of Lp(a) from 163 mg/L to 126 mg/L (23% reduction, P < 0.001), total cholesterol from 5.5 mmol/L to 5.1 mmol/L (7% reduction, P < 0.001), LDL-cholesterol from 4.14 mmol/L to 3.63 mmol/L (12%, P < 0.001), and apo B from 98 mg/dL to 86 mg/dL (12% reduction, P < 0.05), but triglyceride, HDL-cholesterol and apo A-I concentrations were unchanged. These data suggest that L-T4 replacement therapy in patients with subclinical hypothyroidism has beneficial effects on the lipid profile since L-T4 replacement therapy lowered the concentrations of Lp(a) and other atherogenic lipid particles.