The long-term efficacy and potential side effects of oral sympathomimetic amines in the treatment of advanced congestive heart failure remain controversial. We studied the acute and chronic hemodynamic and arrhythmogenic effects of the beta-2 agonist, salbutamol, 6 mg by mouth four times/day, in 20 patients with NYHA classes III to IV congestive heart failure. Acutely, salbutamol increased the cardiac index (1.9 to 2.3 L/min/m2, p less than 0.01) and heart rate (92 to 97 bpm, p less than 0.01) while it decreased pulmonary capillary wedge pressure (35 to 31 mm Hg, p less than 0.01). Salbutamol increased the number of patients having episodes of ventricular tachycardia from two to six and increased the number of episodes of ventricular tachycardia from 2 to 27. Once salbutamol was discontinued, no further episodes of ventricular tachycardia occurred in these six patients. Six patients did not have long-term hemodynamic studies because of serious arrhythmias and two died. In the 12 patients who had long-term studies, the initial beneficial hemodynamic effects of salbutamol were maintained. Thus, although salbutamol may have beneficial long-term hemodynamic effects, it may cause serious arrhythmias in patients predisposed to develop arrhythmias.