Thirty patients undergoing resection of arteriovenous malformations with deliberate hypotension were randomized to receive 1 of 3 hypotensive agents. Anesthesia was maintained with isoflurane and nitrous oxide in all patients. Mean arterial pressure was reduced 20% to 60-65 mm Hg with use of either isoflurane (less than or equal to 4%), sodium nitroprusside (less than or equal to 8 micrograms.kg-1.min-1), or esmolol (less than or equal to 24 mg/min). Esmolol was associated with a decrease in cardiac output from 6.2 +/- 1.3 to 3.8 +/- 0.8 L/min, which, because of a 22% increase in systemic vascular resistance, far exceeded the reduction in mean arterial pressure. Systemic vascular resistance increased despite a 32% decrease in plasma renin activity. In contrast, with sodium nitroprusside or isoflurane, the decrease in mean arterial pressure was associated with decreases in systemic vascular resistance of similar magnitude, with no change in cardiac output. Plasma renin activity levels increased 48% with sodium nitroprusside and 126% with isoflurane. Heart rate increased 13% with sodium nitroprusside, remained unchanged with isoflurane, and decreased 23% with esmolol. Although esmolol may be used as a primary hypotensive agent, the potential for marked myocardial depression must be recognized. The differences in pharmacologic properties for the different hypotensive agents suggest that combinations of these agents may provide a pharmacologic profile superior to either agent alone.