Ventricular arrhythmias are common in patients with congestive heart failure (CHF) and may be exacerbated by positive inotropic therapy. Because human B-type natriuretic peptide (nesiritide), an arterial and venodilator, inhibits sympathetic activity, it may decrease the incidence of arrhythmias. Our investigation compares the arrhythmogenicity of dobutamine with nesiritide. A total of 305 patients with decompensated CHF requiring intravenous vasoactive therapy were randomized to receive standard therapy (n = 102) or nesiritide (0.015 microg/kg/min [n = 103] or 0.030 microg/kg/min [n = 100]) to gain additional data on the relative safety and efficacy of nesiritide compared with standard parenteral care. Dobutamine was chosen as the standard care agent in 58 subjects. During study drug infusion, all patients had continuous clinical hemodynamic and electrocardiographic monitoring. The dobutamine and nesiritide groups were similar with respect to baseline use of antiarrhythmic agents, including beta blockers. Serious arrhythmias and the incidence of cardiac arrest were more common in patients who received dobutamine than in those taking nesiritide: sustained ventricular tachycardia, 4 (7%) versus 2 (1%), respectively (p = 0.014); nonsustained ventricular tachycardia, 10 (17%) versus 23 (11%), respectively (p = 0.029); cardiac arrest, 3 (5%) versus 0, respectively (p = 0.011). We conclude that among patients with decompensated CHF for whom dobutamine is selected as standard therapy, the incidence of serious ventricular arrhythmias and cardiac arrest is significantly greater than the incidence of these events in patients randomized to nesiritide.