Fenoldopam mesylate (SK&F 82526J) (FNP) is a specific postsynaptic dopamine-1 receptor agonist, 1 with weak α 2-antagonistic properties. 2 The agent is devoid of dopamine-2, α-1 or β-adrenergic activity. 3 Fenoldopam functions as an arteriolar vasodilator with dilation in the renal, mesenteric, skeletal muscle and lumbar beds. 4,5 Although a primary effect is through renal vasodilation with consequent increases in renal blood flow, 1–2,4–6 reduction in total peripheral resistance appears to be the mechanism of blood pressure (BP) reduction. 7,8 Furthermore, fenoldopam improves renal blood flow, fractional sodium and free water clearance while lowering BP. 4,9,10 Fenoldopam has a rapid onset (4 minutes) and a short duration of action (<10 minutes) with intravenous administration, 11 and has been reported to be an effective parenteral agent in severely hypertensive patients. 9 The agent undergoes sulfate, methylate and glucuronide conjugation, and produces no accumulation of toxic metabolic or degradation products. 12 Sodium nitroprusside (sodium nitroferricyanide) (NTP) has potent venodilating and arteriolar-dilating properties 13 and in many respects is an ideal antihypertensive agent when rapid reduction of BP is required. NTP quickly and reliably reduces BP in most patients and its short half-life aids in rapid titration of the drug. One major drawback associated with the use of NTP is that the very potency that gives it utility has often led to restrictions on its use. Restrictions include invasive monitoring requirements or use in an intensive care setting, thus dramatically escalating the cost associated with NTP's use. 14 A second drawback is that the formation of thiocyanate degradation products resulting in toxicity has limited its utility. 14 While thiocyanate toxicity has been primarily associated with impaired renal or hepatic function, in which the typical 4-day half-life of thiocyanate is prolonged, reports of toxicity in patients with normal renal function have also occurred. 14 Herein, we compared and evaluated the effects of sodium nitroprusside and intravenous fenoldopam mesylate in an open-label, randomized, multicenter trial of patients with severe systemic hypertension.