Whole-body hyperthermia (WBH) is a well-described investigational adjunct to systemic chemotherapy for the treatment of advanced malignancies. The hemodynamic consequences of this physiologic state may include tachycardia, which can produce acute myocardial ischemia in patients with coronary artery disease. Ischemic heart disease is currently considered a contraindication to WBH. We chose to investigate the consequences of using a new beta 1-adrenergic antagonist, esmolol, to attempt to control the tachycardia associated with WBH. After institutional approval and patient consent, nine consecutive patients with normal cardiac function presenting for WBH with carboplatin infusion were studied. Along with standard monitors, radial arterial and oximetric thermodilution pulmonary artery catheters were placed. Patients were sedated and heated in a radiant warmer (Enthermics). Spontaneous ventilation was maintained and hemodynamic data were gathered at 37 degrees C, and at 41.8 degrees C (before, during and after esmolol infusion). Heart rate and cardiac output increased (by 46% (p = 0.001) and 35% (p = 0.04) respectively) while mean arterial pressure and systemic vascular resistance fell (by 18% (p = 0.02) and 44% (p = 0.006) respectively) during hyperthermia. Heart rate was significantly reduced during esmolol administration (mean dose 180 micrograms/kg/min) in the absence of changes in cardiac index and calculated oxygen delivery. Ventricular filling pressures and stroke work were unchanged. No heart failure, pulmonary edema, or other adverse event was observed. Hemodynamic changes seen during esmolol administration were completely reversed 15 min after the infusion was stopped. We conclude that the administration of moderate doses of esmolol is safe for this population of patients undergoing WBH, and that this technique raises the question of whether patients with ischemic heart disease could safely undergo WBH.