Rilmenidine is a novel antihypertensive agent related to alpha 2-agonists. Pharmacologic and clinical data concerning efficacy and acceptability of rilmenidine, its effects on physiologic functions, and hypothesis of mechanism of action are described in this report. The dominant aspect of rilmenidine is the observed dissociation at therapeutic doses between antihypertensive and central effects. In this respect, several findings resulting from fundamental pharmacology, clinical pharmacology, and therapeutics differentiate rilmenidine from clonidine and related drugs. Hypotheses to explain the results observed with rilmenidine involve unknown properties that could counteract with the alpha 2-adrenoceptor-mediated sedation, respective contribution of central and peripheral components to the activity of rilmenidine, and possible contribution of imidazoline receptors.