Thyroid hormones are now recognized to change in different disease states with important consequences on severity and prognosis of disease. However, little is known about thyroid hormones' alterations in acute liver failure (ALF). To study the changes in thyroid hormones and cardiac thyroid receptors during ALF, we subjected seven female pigs to surgical liver devascularization. Liver function biochemical markers, thyroid hormones, endogenous opioids, malondialdehyde (MDA), and interleukins 1 and 6 were measured in serum for 24 h postoperatively. Heart biopsies were harvested at the end of the experiment. Baseline heart biopsies were taken from five additional animals. Serum thyroxin (T(4)) and triiodothyronine (T(3)) levels markedly decreased, whereas free-triiodothyronine and thyroxin-stimulating hormone levels did not change. T(4) and T(3) levels correlated with the degree of liver failure and with MDA and interleukin-6 levels. Beta-endorphin levels initially increased, whereas levels of leucine-enkephalin did not change. Thyroid hormone receptor-alpha1 protein expression in the heart decreased 1.6-fold after ALF, whereas myocardial myosin isoform expression remained unchanged. The downregulation of T(4) and T(3) levels during ALF seems to correlate well with the severity of disease. This downregulation related to inflammation and oxidative stress and resulted in changes in myocardial thyroid receptors.