Norepinephrine (NE) is considered to exert an important modulatory influence upon the activity of gonadotropin-releasing hormone (GnRH) neurons. In the present study we used a transgenic GnRH-green fluorescent protein mouse model to examine the effects of NE on the electrical excitability of GnRH neurons in male and female mice. Gramicidin-perforated patch recordings demonstrated that NE (10–100µM) exerted a robust membrane hyperpolarization, with associated suppression of firing, in >85% of male prepubertal and adult GnRH neurons (n= 25). The same hyperpolarizing action was observed in female GnRH neurons from diestrous (91%, n= 11), proestrous (50%, n= 14), estrous (77%, n= 13) and ovariectomized mice (82%, n= 11). A sub-population (<10%) of silent GnRH neurons in all groups responded to NE with hyperpolarization followed by the initiation of firing upon NE washout. The hyperpolarizing actions of NE were mimicked by 1 (phenylephrine) and (isoproterenol) adrenergic receptor agonists, but 2 receptor activation (guanabenz) had no effect. Approximately 75% of the NE-evoked hyperpolarization was blocked by the 1 receptor antagonist prazosin, and 75% of GnRH neurons responded to both phenylephrine and isoproterenol. These findings indicate that NE acts through both 1 and adrenergic receptors located on the soma/dendrites of GnRH neurons to directly suppress their excitability throughout the estrous cycle and following ovariectomy. These data force a re-analysis of existing models explaining the effects of NE on gonadotropin secretion.