The excitability of vasopressin-secreting neurons in the hypothalamic supraoptic nucleus is transiently depressed by an abrupt increase in arterial pressure sufficient to activate peripheral arterial baroreceptors. The present experiments examined the ability of locally applied transmitter antagonists to alter this response. Extracellular data were obtained from 27 supraoptic vasopressin-secreting neurons in pentobarbital-anesthetized male Long-Evans rats. In seven of eight cells tested, bicuculline (100 microM) reversibly abolished or delayed the anticipated cessation in neuronal firing that accompanied a 40- to 60-mmHg increase in arterial pressure induced by a brief intravenous infusion of the alpha-agonist metaraminol. Similar tests applied to the remaining cells revealed that prazosin (10 microM), timolol (20 microM), or strychnine (100 microM) were ineffective. These findings suggest that gamma-aminobutyric acidA receptors mediate the depressant responses observed among supraoptic vasopressin-secreting neurons consequent to peripheral baroreceptor activation.