In order to investigate the influence of the thymus on liver functions, we used adult thymectomized rats as a model and supplemented the animals with either thymic extracts or sex hormones. Male thymectomized rats exhibited a decrease in liver microsomal cytochrome P-450 and aminopyrine-N-demethylase activities. There was also a decrease in the levels of hypothalamic luteinizing hormone-releasing hormone (LHRH), plasma luteinizing hormone (LH) and testosterone. Supplementation of testosterone propionate to these animals restored their liver P-450 and demethylase activities to normal levels. Female thymectomized rats showed an increase of liver malondialdehyde (MDA), accompanied by a decrease of liver superoxide dismutase (SOD) and glutathione (GSH), and a decline of fluidity and calcium ion uptake in liver microsomal and mitochondrial membranes. There was also a decline in hypothalamic LHRH and plasma estradiol. Supplementation of thymic extract to female thymectomized rats decreased the liver MDA, increased the liver GSH, and restored the microsomal and mitochondrial membrane fluidity and calcium ion uptake. The decrease of liver MDA was also achieved by administration of estradiol benzoate. The data suggest that the thymus may influence liver functions through the hypothalamus-pituitary-gonad axis. Thus, a new 'thymus-neuroendocrine-liver pathway' is proposed that further affirms the significance of the thymus on maintaining homeostasis and integrative functions in the body.