Acute anxiety reactions have been reported following antagonism of benzodiazepine-induced sedation. In this study, the level of sedation and anxiety was assessed in 30 patients randomly assigned to receive either saline or flumazenil (a benzodiazepine antagonist) after midazolam sedation according to a double-blind protocol. Carefully titrated doses of flumazenil, 0.8 ←+ 0.2 mg (mean ± SD), effectively reversed residual midazolam-induced sedation without producing significant changes in the patients' level of anxiety. In addition, plasma epinephrine, norepinephrine, vasopressin, and β-endorphin concentrations were measured in a subset of patients (n = 5) from each group. The levels of these stress hormones did not acutely change following flumazenil (or saline). These results indicate that flumazenil, 0.6-1.0 mg iv., can antagonize midazolam sedation without producing acute anxiety or evidence of a stress response.