Dexamethasone, a corticosteroid used to treat cerebral edema, is known to produce elevations in the blood glucose concentration, but the effect of a single intraoperative dose of dexamethasone on the blood glucose concentration is unknown. Glucose concentrations in response to either a 10-mg intravenous bolus of dexamethasone or a saline placebo were evaluated in nondiabetic patients undergoing elective craniotomy. Both arterial and venous blood glucose concentrations were obtained immediately before and after treatment and hourly for 4 hours intraoperatively. The arterial blood glucose concentration in those who received 10 mg dexamethasone (n = 10) increased from 97 +/-15 mg/dL (mean +/- SD) to 149 +/- 23 mg/dL over the course of the study, compared with a change from 88 +/- 11 mg/dL to 103+/-12 mg/dL in those who received placebo (n = 10) (P < 0.05 for 4-hour sample vs. baseline for both groups; P < 0.05 between groups at 4 hours). Further, venous blood glucose concentrations were highly predictive of arterial glucose values (R = 0.98; P < 0.001). Since elevations in the blood glucose concentration should be avoided in the setting of central nervous system ischemia, findings from this investigation suggest that contemplated corticosteroid use should be reviewed for appropriateness of treatment. If dexamethasone is used, even as a single dose during craniotomy, intraoperative blood glucose concentrations should be carefully monitored and hyperglycemia treated, particularly in patients at risk for glucose-mediated exacerbation of brain injury.