Fourteen patients with refractory congestive heart failure (CHF) were given a single oral dose ranging from 5 to 30 mg of the new sympathomimetic drug pirbuterol. Hemodynamic measurements and plasma pirbuterol levels were obtained at control and then serially for 6 hours following drug administration. The optimal pirbuterol dose range was determined to be 20 to 30 mg. Ten patients received 20 to 30 mg pirbuterol. In this group cardiac index was significantly increased (1.9 to 2.6 L/min/m2, p < 0.001). Pulmonary artery wedge pressures fell significantly (24 to 20 mm Hg, p < 0.02). Decreases were also noted in mean pulmonary artery pressure (36 to 31 mm Hg, p < 0.02), aortic diastolic pressure (71 to 65 mm Hg, p < 0.05), systemic vascular resistance (1782 to 1201 dynes · sec · cm-5, p < 0.001), and pulmonary vascular resistance (265 to 175 dynes · sec · cm-5, p < 0.001). Systolic and mean aortic pressure and heart rate showed no significant change from control. Hemodynamic effects persisted for 5 hours. Pirbuterol was clinically well tolerated. The mechanism of action is unclear at this time, but both inotropic and vasodilator effects are possible. Pirbuterol orally has a marked and prolonged salutary hemodynamic effect and offers promise in CHF treatment.