Despite the growing popularity of vasodilator therapy for acute and chronic congestive heart failure (CHF), no single agent has been uniformly effective and well tolerated. Therefore, we investigated the acute hemodynamic response to diazoxide, a potent and long-acting arteriolar dilator, in nine patients with severe CHF refractory to conventional treatment and, in seven of nine, other vasodilators. Diazoxide was administered intravenously in successive 300 mg infusions, each over 10 minutes, until a satisfactory response in cardiac and output occurred or a fall in arterial blood pressure or increase in heart rate was noted. The mean dose of diazoxide was 670 mg (range 450 to 900 mg). Systemic vascular resistance fell immediately, by a maximum of 44%. Arterial pressure was not changed significantly, but cardiac and stroke volume indices rose by 64% and 49%, respectively, from 2.0 +/- 0.5 to 3.3 +/- 0.6 L/min/m2 and from 24 +/- 10 to 36 +/- 9 ml/m2 (each p less than 0.001). Pulmonary capillary wedge pressure declined more gradually, by a mean of 8 mm at 4 and 6 hours after drug infusion. This hemodynamic improvement was sustained for a mean of 9.7 hours (range 6 to 12 hours). Our findings indicate that intravenous diazoxide may be useful in the management of acute heart failure and that a trial of oral diazoxide in chronic normotensive CHF is warranted.