Despite successful therapies for chronic hypertension, hospital admissions for hypertensive emergency more than tripled between 1983 and 1992. Objective: To examine the safety and efficacy of fenoldopam, the first antihypertensive with selective and specific action on vascular dopamine (DA1) receptors, in a clinical trial involving emergency department patients with true hypertensive emergencies. Methods: Patients with a sustained diastolic blood pressure (DBP) of ≥120 mm Hg and evidence of target organ compromise were randomized in a double-blinded manner to one of four fixed doses of intravenous fenoldopam (0.01, 0.03, 0.1, or 0.3 μg/kg/min) for 24 hours. The primary endpoint was the magnitude of DBP reduction in each of the three higher-dose groups after four hours of fenoldopam treatment compared with the lowest-dose group. Results: One hundred seven participants from 21 centers were enrolled, and 94 patients received fenoldopam. Evidence of acute target-organ damage included new renal dysfunction or hematuria (50%), acute congestive heart failure or myocardial ischemia (48%), and papilledema or grade III-IV hypertensive retinopathy (34%). The DBP decreased in a dose- dependent fashion, with significant differences between the 0.1- and 0.3- μg/kg/min groups compared with the lowest-dose group. Treatment was well tolerated, and there were no deaths or serious adverse events during follow- up, up to 48 hours. All patients were successfully transitioned to oral or transdermal antihypertensives with maintenance of blood pressure control. Conclusions: Fenoldopam safely and effectively lowers blood pressure in a dose-dependent manner in patients with hypertensive emergencies. Observations supporting potential risk factors for hypertensive emergency are discussed.