In hypothyroidism, lack of thyroid hormones results in reduced cardiac function (cardiac output [CO]), and an increase of systemic vascular resistance (SVR). We speculated whether hemodynamic regulation in subjects with subclinical hypothyroidism (SH) (defined as mildly elevated thyrotropin [TSH] despite free thyroxine [T(4)] and triiodothyronine [T(3)] estimates within reference range) would benefit from levothyroxine (LT(4)) substitution. CO was measured by impedance cardiography, which is an observer independent method with high precision, and mean arterial pressure (MAP) by oscillometry. SVR was then calculated as MAP/CO. Measurements were performed before and after 60 degrees head-up tilting, and before and after LT(4) substitution. Plasma levels of catecholamines were also measured. In 16 otherwise healthy women with SH (ages 44-74 years; serum TSH in mean 17.1 mU/L (range, 6.8-27), and normal free T(4) and T(3) estimates) LT(4) treatment resulted in 6% reduction in supine MAP (p <0.01), 14% increase in upright CO (p <0.05), and 13%-20% decrease in SVR (supine and upright position, respectively) (p <0.05). Plasma norepinephrine as well as epinephrine decreased during LT(4) treatment (p <0.05). These changes were qualitatively similar but quantitatively less pronounced than in 15 women with overt hypothyroidism, also studied. Taking the two groups together (n = 31), pretreatment thyroid function (expressed as either TSH or free T(4) estimate) correlated to CO and SVR as well as the changes induced by LT(4) (p <0.05), i.e., the lower the thyroid function the lower the CO and the higher the SVR, and the greater the response to LT(4). We conclude, that LT(4) treatment in SH results in changes in hemodynamic parameters of potentially beneficial character. SH and overt hypothyroidism should be regarded as a continuum, and our data favor earlier and more aggressive treatment of SH.