1. This study evaluated the influence of focal electrical and chemical microstimulation in the median preoptic nucleus (MnPO) on the excitability of putative vasopressin and oxytocin neurones recorded in the supraoptic nucleus of urethane- or pentobarbitone-anaesthetized rats. 2. In vasopressin neurones, single 1 Hz stimulation reduced the excitability of 120/139 cells. Trains of repetitive 5-30 Hz stimulation, or microinfusion of glutamate into the MnPO, similarly induced a cessation in spontaneous phasic or continuous firing in 17/18 and 17/20 vasopressin neurones, respectively. In 20/21 cells, locally applied bicuculline (100 microM) attenuated MnPO-evoked depressant responses whereas strychnine (100 microM) and timolol (20 microM) were without effect on 5/5 vasopressin neurones. In three cells, bicuculline applications were associated with marked increases in MnPO-evoked excitations. 3. In oxytocin neurones, single-pulse (1 Hz) electrical stimulation in MnPO evoked an increase in the excitability in 51/59 cells. However, in 6/7 oxytocin cells tested, glutamate microinfusions into MnPO induced prolonged suppression in firing. During trains of stimuli (5-30 Hz), 26/44 cells displayed an initial increase in firing associated with the first few impulses but this was then replaced by suppression of activity; another ten cells displayed excitation alone, and eight cells demonstrated only suppression. The depressant responses evoked during trains of MnPO stimulation were blocked by 100 microM bicuculline (6/6 cells tested) whereas strychnine was ineffective (2/2 cells tested). 4. These results suggest that the MnPO provides a mainly depressant influence on supraoptic vasopressin and oxytocin neurones, perhaps through the activation of postsynaptic GABAA receptors.