Previous studies suggest that the hypotensive response to centrally administered propranolol results from a drug-induced release of norepinephrine which then stimulates central alpha adrenergic receptors and, as a consequence, arterial pressure is lowered. Inasmuch as the C1 area of the rostral ventrolateral medulla is known to contain noradrenergic nerve terminals and participate in arterial pressure regulation, we determined whether this medullary region is a site mediating the hypotensive response to centrally administered propranolol. Bilateral microinjections (0.1 microliter) of dl-propranolol (0.25-2 nmol) into the C1 area of urethane-anesthetized rats resulted in a gradual reduction in mean arterial pressure which was sustained throughout the 120-min experimental period. The injection site was verified pharmacologically at the end of each experiment by bilateral microinjection of 10 nmol of tyramine and observing a further decrease in mean arterial pressure and a reduction in heart rate. Pretreatment of the C1 area bilaterally with reserpine 24 hr earlier significantly reduced the hypotensive responses to microinjections of both propranolol and tyramine whereas the hypotensive response to the direct acting agonist clonidine was unchanged. These results demonstrate that the C1 area of the rostral ventrolateral medulla is a site for a central hypotensive action of propranolol. Moreover, the data provide further evidence that the hypotensive action of centrally administered propranolol results from a drug-induced release of norepinephrine from central noradrenergic neurons.