Since the first report of folliculo-stellate cells as corticotrophs by Farquhar , their histological characteristics have been investigated by many researchers. However, the physiological significance of folliculo-stellate cells has not been clearly elucidated so far. The present study is designed to investigate the function of folliculo-stellate cells, particularly focusing on their responses to LH-RH. Changes in the intracellular concentration of calcium ions ([Ca2+]i) were measured from folliculo-stellate cells in the “transitional zone” of the anterior pituitary gland. The anterior pituitary glands were removed from 7 weeks old male Wistar rats weighing 250 - 300 g. One group was used for immunohistochemical study to detect the distribution of S- 100 protein and LH-RH protein, and the other group was employed for electron microscopic examination. The remaining tissues were used for Ca measurements. Under Nomarski optics, areas of cells which corresponded to either granular cells or agranular, folliculo-stellate cells were marked. Changes in [Ca2+]i from selected areas were then measured using fura-2 loaded preparations. Bath-applied LH-RH (100 μg/ml) caused transient increases in [Ca2+]i which were followed by sustained increase in [Ca2+]i either with or without Ca oscillations. These results demonstrated that not only granular but also agranular folliculo-stellate cells, may be capable of responding to LH-RH by increasing [Ca2+]i, and thus intracellular Ca may play an important role in regulating the function of folliculo-stellate cells upon LH-RH stimulation. We hypothesize that the LH-RH message from the brain entered the anterior lobe via the “transitional zone” and then spread throughout the gland mediated via by a network system of folliculo-stellate cells as well as the portal vascular system.