While peptidergic nerve fibers have been immunoreactively identified in the adenohypophysis of mammals, the function of these fibers in the regulation of hormone secretion remain unknown. The present work was undertaken to investigate possible modulating effects of these fibers on the secretion of ACTH in the anterior pituitary. Electrical field stimulation (EFS) was applied to excite the nerve terminals in anterior pituitary quarters of male rats under static incubation, and the ACTH level was determined by radioimmunoassay. It was found that the ACTH release from the anterior pituitary was significantly enhanced by EFS (30 mA, 0.5 ms and 10 Hz), which could be significantly decreased by adding TTX or veratridine into the incubation medium. However, TTX failed to inhibit AVP-induced ACTH secretion. Since the dispersed cultured anterior pituitary cells did not respond to the same EFS, it was suggested that there might exist dual modulatory mechanisms on the anterior pituitary hormone secretion.