Experiments were undertaken in urethane-anaesthetized rats to investigate the effects of systemic clonidine on the firing of supraoptic vasopressin (VP) neurones, which were identified by their characteristic phasic activity pattern. Injection of clonidine (50 micrograms/kg i.v.) reduced the firing of all 16 VP neurones tested, and their overall mean activity decreased from 5.09 +/- 1.01 to 1.63 +/- 0.64 spikes/second (P < 0.02). In VP cells which were already firing phasically before clonidine, the inhibition resulted in complete quiescence. In VP cells which were originally continuously active, the inhibition resulted in a switch to phasic activity. This inhibitory effect, which was prevented by prior injection of the alpha-2 antagonist idazoxan (0.5 mg/kg), had a mean duration of 11.8 +/- 1.8 min. Subsequent experiments revealed that i.v. clonidine (50 micrograms/kg) caused a transient rise in blood pressure, but this had a shorter time-course and was unlikely to account for the prolonged neuronal inhibition. It was concluded that systemic clonidine acts centrally to suppress the activity of hypothalamic VP neurones, thereby explaining the fall in plasma VP levels found in previous studies.