Activation of the pituitarythyroid system was induced in adult female rats by electrical stimulation of the anterior hypothalamus and rostral portion of the median eminence. A series of bilateral stimulations given to these brain areas (20 min daily, 4 successive days) effected significant increases in serum TSH (stasis tadpole method of bio-assay) to levels which were 3–4 times greater than that found in sham-stimulated controls. The rise in circulating thyrotrophin was correlated with histologic alterations in the thyroid gland indicative of increased function. These effects were not observed in hypothalamic-lesioned rats receiving equivalent periods of electrical stimulation, nor in normal animals given only one 20-min period of excitation to the intact hypothalamus. The results clearly demonstrate a specific role for the anterior hypothalamus and median eminence in the release of TSH from the pituitary and provide evidence for the physiologic concept of a hypothalamo-hypophysialthyroid system.