The effects of d-, l-, dl-propranolol HCl and isoproterenol HCl on mean arterial blood pressure, heart rate and respiration were examined in 83 urethane-anesthetized, spontaneously hypertensive rats with carotid arterial and femoral venous catheters and stereotaxically positioned hypothalamic-thalamic cannulae. All three propranolol compounds produced a significant decrease in both blood pressure and respiratory rate when they were instilled into the posterior hypothalamic region and/or the pars magnocellularis region of the ventral medial thalamus. Isoproterenol produced an immediate (8 to 20 sec) depressor response following instillation in the hypothalamic-thalamic region but had no immediate effect when it was instilled in the reticular formation. Isoproterenol also did not produce any significant change in mean arterial blood pressure, heart rate or respiratory rate when it was administered centrally 15 min after instillation of either l- or dl-propranolol. The central antihypertensive activity of isoproterenol was not blocked following central administration of d-propranolol. The results suggest that cells located in the posterior hypothalamic-ventral medial thalamic region send projection fibers directly or indirectly to the cardiovascular and respiratory centers located in the brain stem. The results also suggest that the central antihypertensive activity of d-propranolol is probably due to local anesthetic activity while the activity of l-propranolol may be a reflection of central adrenoceptor blockade which may or may not include a local anesthetic component.