Cardiovascular and behavioral responses to circulating angiotensin require intact connectivity along the upper lamina terminalis joining the subfornical organ (SFO) with the median preoptic nucleus (MnPO). Whole cell patch-clamp recordings in sagittal rat brain slice preparations revealed that 28/40 MnPO neurons responded to electrical stimulation of SFO efferents with bicuculline-sensitive GABAA receptor-mediated inhibition and glutamate-mediated postsynaptic excitation involving AMPA and N-methyl-d-aspartate (NMDA) receptor subtypes, blockable with 2,3-dioxo-6nitro-1, 2,3,4-tetrahydrobenzo [f] quinoxaline-7-sulfoamide disodium (NBQX) and d-2-amino-4-phosphonovaleric acid (d-APV), respectively. Bath applications of baclofen induced a concentration-dependent (0.3–10 μM) reduction in these SFO-evoked postsynaptic currents, attenuation of SFO-evoked paired-pulse depression, and reduction in frequency (but not amplitude) of miniature postsynaptic currents, consistent with an action at presynaptic GABAB receptors. Baclofen's effects on miniature currents lacked sensitivity to barium, ω-conotoxin GVIA, and cadmium. Acting at postsynaptic GABAB receptors, baclofen hyperpolarized a majority of MnPO neurons by increasing a G protein–coupled inwardly rectifying potassium conductance and suppressing an N-type high-voltage–activated calcium conductance. The latter contributed to reduction in action potential afterhyperpolarization and enhanced cell firing and spike frequency adaptation when tested with a depolarizing stimulus. All baclofen-induced effects were blockable with CGP52432 . CGP52432 alone had no significant effect on SFO-evoked postsynaptic current amplitudes or paired-pulse ratios, but did induce an increase in miniature inhibitory postsynaptic current (mIPSC) frequency in 2/4 cells tested, indicating that ambient levels of GABA could activate presynaptic GABAB receptors on undefined inputs. These observations indicate that MnPO neurons receive both a GABAergic and glutamatergic innervation from SFO. Both forms of rapid neurotransmission are subject to modulation via pre- and postsynaptic GABAB receptors.