Animal studies suggest that hyperglycemia (glucose concentrations > 225 mg/dl) occurring prior to periods of brain ischemia exacerbates neurologic damage. Neurosurgical patients, a group at risk for intraoperative brain ischemia, often receive glucose. Therefore, the effects of intraoperative glucose administration (IGA) on these patients were studied. Sixteen patients undergoing supratentorial craniotomy were randomly assigned to receive either 5% glucose in 0.9% sodium chloride solution (G) or 0.9% sodium chloride solution (S) infusion (both at a rate of 3–4 ml · kg−1· h−1) during the first 4 h of surgery. All patients received glucose infusions postoperatively. Plasma glucose, insulin, free fatty acids, alanine, ketones, base excess,pH, triglycerides, and lactate were measured during the infusion period and 24 h postoperatively. Urinary nitrogen was measured, commencing with the infusion and continuing for 24 h. Neurologic testing included preoperative and postoperative neurologic and psychomotor exams, time to extubation (min), and degree of alertness at the completion of anesthesia. The G group had significantly greater intraoperative plasma glucose concentrations at all time periods studied during the infusion (P< 0.05). Glucose levels ranged from 200–242 mg/dl compared with 12–160 mg/dl in G and S groups, respectively. G group hyperglycemia was within the range associated with exacerbation of ischemic brain damage in animal studies. Free fatty acids and ketones were significantly greater (P< 0.05) intraoperatively in the S group. Lactate and insulin were significantly greater in the G group at 4 h. Total urinary nitrogen was comparable in both groups but was significantly greater intraoperatively (P< 0.05) in the G group (13 ± 2vs.7 ± 1 mg · kg−1· h−1). No differences in the other metabolic indices were found. Likewise, no difference between groups was found in the neurologic variables; however, the number of patients studied was small. In summary, IGA produced plasma levels that have been associated with potentiation of ischemic neurologic damage, while patients receiving saline had much lower glucose levels. Because there does not appear to be any metabolic compromise in those not receiving glucose, the results suggest that glucose should be avoided during intracranial surgery.