We utilized luteinizing hormone-releasing hormone (LHRH) secretion by perifused minced rat hypothalamic median eminence (ME) tissue to evaluate whether isotonic ethanol would stimulate neurosecretion as it does secretion from pituitary cells. Isotonic ethanol induced a dose-dependent burst of LHRH secretion which was maximal at 2-3 min and returned to near baseline by 10 min. In Ca(2+)-depleted media (< 2 microM Ca2+), stimulation of secretion by isotonic ethanol was enhanced, but secretion induced by depolarizing 30 mM K+ was abolished. Hypertonic ethanol was ineffective in stimulating LHRH secretion in either normal or Ca(2+)-free media. The secretory response of hypothalamic LHRH-secreting cells to ethanol and its negative modulation by medium Ca2+ is thus identical to that of normal anterior pituitary cells and presumably is caused by cell swelling resulting from influx of permeant ethanol molecules across the plasmalemma.