Cicletanine ((+/-)3-(4-chlorophenyl)-1,3-dihydro-7-hydroxy-6-methylfuro-[3,4-c ] pyridine) 3-(4-chlorophenyl)-1,3-dihydro-7-hydroxy-6-methylfuro-[3,4-c] pyridine) is a novel antihypertensive agent that has been shown to possess vasorelaxant, natriuretic, and diuretic properties in preclinical and clinical studies. The mechanism(s) by which cicletanine induces these biological effects has not been definitely established, although it appears to differ from that of other classes of antihypertensive drugs. The salidiuretic activity appears to be the result of an action of the sulfoconjugated metabolite of cicletanine, which inhibits the apical Na+-dependent Cl-/HCO3- anion exchanger in the distal convoluted tubule. The mechanism of the vasodilating effect of cicletanine seems to be complex; it may include stimulation of vascular prostaglandin synthesis, inhibition of the low Km cyclic GMP phosphodiesterases, and blockade of Ca2+ channels either directly or indirectly through a K+-channel opening effect. The drug has also been shown to interact with alpha-adrenergic, vascular histamine, and muscarinic receptors. We have also reviewed the other vascular effects of the drug, such as stimulation of nitric oxide synthesis and inhibition of both myosin light chain kinase and protein kinase C. Cicletanine protects cardiovascular and renal systems against the injuries induced by hypertension, in addition to its lowering of arterial pressure. Similarly to the vasorelaxant action of cicletanine, the various properties of the drug likely contribute to its protective effect against injury in hypertension.