In rat, anaesthetized with urethane and paralyzed, bilateral microinjections of histamine or naphazoline into a region of the rostral ventrolateral medulla (RVL) containing adrenergic neurons of the C1 group (C1 area) elicited a dose-dependent, anatomically specific and reversible decrease of arterial pressure (AP) and heart rate (HR). Similar effects were observed with the histamine agonists 4-imidazole acetic acid or the selective H2 agonist dimaprit. The selective H2 antagonist metiamide but not the H1 antagonist chlorpheniramine injected bilaterally into the C1 area reversibly blocked the hypotension and bradycardia elicited by histamine or dimaprit without affecting the responses produced by naphazoline. Neither metiamide nor chlorpheniramine change resting AP or HR. Pretreatment of the C1 area with the non-imidazole alpha-adrenoceptor blocker phenoxybenzamine while increasing resting AP and HR, antagonized the decrease of AP and HR elicited by the indirect sympathomimetic agonist tyramine but not those by histamine. We conclude, that histaminergic and tonic noradrenergic mechanisms coexist in the C1 area of the RVL mediating sympathoinhibitory responses, the effect of histamine is mediated by H2 but not by H1 receptors.