BACKGROUND: Cicletanine bydrochloride is a newly developed anti-hypertensive agent. The presence of a furopyridine group characterizes its uncommon chemical structure as an antihypertensive molecule. This clinical trial was performed to confirm the efficacy and safety of cicletanine for the treatment of hypertension as a monotherapy. METHODS: In order to investigate the efficacy and safety of oral cicletanine, a now class of antihypertensive durgs, the furopyridines, on essential hypertension, a single daily dose of 50mg to 100mg cicletanine was administered in 46 hypertensive patients with diastolic blood pressure in the range of 95mmHg-115mmHg. The patients were asked to cut off other anti hypertensive agents for 10 weeks prior to this clinical trial. Blood pressure and heart rate were measured every 4 weeks. The complete blood count, blood chemistry done by SMA-12, serum electrolytes and urinalysis were performed at the 12th week of therapy. RESULTS: 1) Baseline blood pressures after 2 weeks of placebo at sitting and standing positions were 158.7+/-16.1/102.9+/-6.2 and 148.7+/-14.5/102.7+/-6.7mmHg, respectively. The overall slope which represents the tendency of blood pressure decline over the treatment period with cicletanine for all the patients in each position are as follows ; -0.726(SE : 0.150) for sitting systolic blood pressure(BP), -0.390(SE : 0.080) for sitting diastolic BP, -0.214(SE : 0.183) for standing systolic BP and -0.341(SE : 0.139) for standing diastolic BP. 2) The slope of sitting systolic BP line in cicletanine 100mg treated group was significantly stiffer than that of cicletanine 50mg treated group(-0.445 vs -1.021, p=0.0336). 3) There were no significant interval changes in heart rate over the treatment period. 4) There were no significant interval changes in blood chemistry, electrolytes, hematologic findings and urinalysis over the treatment period. 5) Several side effects were observed in six patients(epigastric discomfort in 4, easy fatigue and insomnia in one patient, respectively). CONCLUSION: Treatment with cicletanine was well-tolerated and the incidence of side effects was relatively low. Because of its unique anti-hypertensive mechanism and moderated antihypertensive effects, cicletanine may be well suited in the treatment of hypertension combined with other classes of antihypertensive agents.