1 We investigated the actions of the endogenous opioid tetra-peptide endomorphin 1, a selective mopioid receptor agonist, on oxytocin and vasopressin cell activity in vivo and in vitro. 2 The activity of antidromically-identi®ed supraoptic nucleus cells were recorded from urethaneanaesthetized female rats. The ®ring rates of both oxytocin and vasopressin cells were reduced by intracerebroventricular endomorphin 1 (5 ± 100 pmol); this inhibition was prevented by intravenous naloxone (5 mg kg 71 ). 3 A second group of rats was infused intracerebroventricularly with endomorphin 1 (27 pmol min 71) over 5 days. The ®ring rates of oxytocin and vasopressin cells in endomorphin 1 pre-treated rats were similar to those of endomorphin 1 naõÈ ve rats, indicating tolerance to the inhibitory eects of endomorphin 1. Intravenous naloxone induced similar modest and transient increases in the ®ring rate of oxytocin cells in endomorphin 1 pre-treated rats and endomorphin 1 naõÈ ve rats, indicating that endomorphin 1, unlike the m-opioid alkaloid agonist, morphine, does not induce m-opioid dependence in these cells. 4 In vitro, whole-cell current clamp recordings were made from supraoptic nucleus cells in superfused coronal hypothalamic slices from young female rats. Endomorphin 1 (100 nM) inhibited the ®ring rate of oxytocin cells but had no signi®cant eect on vasopressin cells at up to 10 mM. Inhibition of oxytocin cells was reversed by naloxone, and remained when synaptic transmission was blocked by superfusion with low Ca