Background and Purpose Hypertensive hypervolemic therapy has been shown to reverse delayed ischemic deficits after aneurysmal subarachnoid hemorrhage. Concern has been raised about systemic complications of therapy, including pulmonary edema and myocardial ischemia, especially when high doses of vasopressors are used. Patients in whom delayed ischemic deficits were treated with hypervolemia and phenylephrine were prospectively evaluated for signs of systemic toxicity. Methods Twenty-four consecutive patients treated with hypertensive hypervolemic therapy after aneurysmal subarachnoid hemorrhage were studied. Sixty-seven percent had underlying cardiac disease, vascular disease, or hypertension. No patient was excluded because of age or preexisting cardiac disease. Patients were closely monitored for signs of congestive heart failure (physical examination, chest x-ray films, arterial blood gases, cardiac index, pulmonary artery wedge pressure, and oxygen requirement). Indicators of cardiac ischemia and other extracerebral toxicity that were monitored included cardiac enzymes, electrocardiograms, serum creatinine, electrolyte and lactic acid levels, gastrointestinal motility, and urine output. Results Volume expansion and phenylephrine infusion produced an increase in several hemodynamic parameters including pulmonary artery wedge pressure, which rose 28% (13 plus minus 3.6 to 16 plus minus 1.9 mm Hg), mean arterial blood pressure, which rose 25% (99 plus minus 12.5 to 123 plus minus 11.4 mm Hg), and systemic vascular resistance, which rose 46% (1234 plus minus 294 to 1739 plus minus 315 dyne centered dot sminus 1 centered dot cmminus 5); however, there was no change in cardiac index (3.9 plus minus 0.9 to 4.0 plus minus 0.6 L centered dot minminus 1 centered dot mminus 2). There were no clinically significant episodes of pulmonary edema requiring a change in vasopressor therapy and no myocardial infarctions. Phenylephrine was stopped in only one patient (incidence, 4%; 95% confidence interval, 0% to 12%), who developed an exacerbation of his preexisting bradycardia. There was no evidence of noncardiac organ system toxicity. Eighty-eight percent of the patients exhibited neurological improvement. Conclusions Hypertensive hypervolemic therapy with the use of high-dose phenylephrine can be administered with acceptable systemic toxicity, even in patients with previous cardiac disease, provided that close monitoring is performed. To minimize risk, aggressive treatment should probably be reserved for patients with signs of delayed ischemia rather than administered prophylactically.