The role of alpha 2-adrenoceptors in the central regulation of blood pressure has been questioned, since drugs such as clonidine stimulate both alpha 2-adrenoceptors and imidazoline-preferring receptors. The present work was undertaken to study the influence of alpha 2D-adrenoceptors, encoded by the RG20 gene, on blood pressure in the rat. An antisense phosphodiester oligodeoxynucleotide, directed at nucleotides 4-21 of the RG20 gene, was injected in the right lateral cerebral ventricle, causing an increase in systolic blood pressure, both at 1 and 2 days after the injection, when compared to groups of control rats (injected with the sense oligodeoxynucleotide or a missense oligodeoxynucleotide or distilled water). Antisense oligodeoxynucleotides directed either at nucleotides 65-82 of the RG10 gene (encoding for alpha 2C-adrenoceptors) or at nucleotides 26-43 of the RNG gene (encoding for alpha 2B-adrenoceptors), failed to produce any change in blood pressure after being injected. We conclude that the alpha 2-adrenoceptor encoded by the RG20 gene may play a role in blood pressure regulation in the rat.