We have used hypothalamic slices of the supraoptic nucleus (SON) to investigate synaptic control of magnocellular vasopressinergic and oxytocinergic neurons. With the use of perforated patch recording techniques we identified and isolated excitatory or inhibitory postsynaptic currents elicited by electrical stimulation of afferent fibers. Both inhibitory and excitatory afferent fibers displayed presynaptic GABAB receptors; the GABAB agonist, baclofen caused a dose-dependent suppression of the evoked potentials in the absence of any effects on postsynaptic input resistance. Further evidence for a presynaptic locus included an increase in paired pulse ratio and a lack of effect on currents elicited by exogenously applied muscimol (a GABAA receptor agonist) or AMPA (a glutamate agonist). With the use of an GABAB receptor antagonist we demonstrated an action of endogenously released GABA, acting at GABAB receptors on excitatory terminals, to reduce excitatory transmission. In addition to presynaptic modulation by GABA of afferent inputs, we also observed actions of vasopressin and oxytocin, released from dendrites of magnocellular SON neurons, to gate afferent, excitatory transmission in the SON. Exogenously applied vasopressin and oxytocin, or these peptides when released by depolarizing stimuli of magnocellular neurons, reduced the size of evoked excitatory postsynaptic potentials at a presynaptic locus. We have also observed actions of arginine vasopressin to modulate the action of glutamate in slices of the ventral septal area and to attenuate a glutamate-mediated excitatory postsynaptic current in slices of the parabrachial nucleus.