Congestive heart failure patients with severe pulmonary hypertension are at risk of death from acute right ventricular failure of the donor heart in the early postoperative period after orthotopic cardiac transplantation. Therefore in the preoperative evaluation of these patients, it is extremely important to determine whether pulmonary hypertension can be reversed by pharmacologic means. Patients with reactive pulmonary hypertension can be considered suitable for orthotopic transplantation and the effective drug utilized postoperatively to reverse pulmonary hypertension and prevent failure of the donor right ventricle. To determine which pharmacologic agent is most effective in reversing pulmonary hypertension in congestive heart failure, the acute pulmonary hemodynamic effects of comparable doses of direct intravenous vasodilators including nitroglycerin, nitroprusside, and prostaglandin E1, and intravenous inotropic agents dobutamine and enoximone, were evaluated in 66 patients undergoing cardiac transplantation evaluation. All drugs significantly increased cardiac output and decreased calculated pulmonary vascular resistance. All drugs except dobutamine significantly lowered pulmonary artery and pulmonary artery wedge pressures. Prostaglandin E1 was the only drug that significantly lowered transpulmonary pressure gradient (pulmonary artery mean pressure minus mean pulmonary wedge pressure). The magnitude of decline of pulmonary vascular resistance and transpulmonary pressure gradient was greatest with prostaglandin E1 compared with other drugs. These observations indicate that prostaglandin E1 may be more effective than the other studied drugs for acute reversal of pulmonary hypertension in congestive heart failure.