Abstract The possible participation of the medial medullary reticular formation (MMRF) in clonidine-induced hypotension has been investigated in lightly pentobarbital sodium (40 mg/kg, i.p.) anaesthetized rats. Bilateral focal electrolytic lesions of the MMRF resulted in an elicited hypertension without the subsequent hypotension normally observed when clonidine (10 μg/kg) was injected systemically. On the other hand, muinjection of clonidine, at an ineffective dose (0.25 μg/kg) when administered intravenously, induced a significant vasodepression with no preceding hypertension. While confirming that clonidine exerts its pressor effects by acting peripherally, this study has identified the MMRF as at least one of the central sites through which clonidine may produce depression of arterial blood pressure. The role of the MMRF has been attributed to modulation of basic circulatory reflexes. When activated by clonidine, the reticular neurones may inhibit the sympathetic discharges and facilitate the parasympathetic outflow to the cardiovascular effectors, resulting in clonidine-hypotension of central origin.