Flumazenil, a specific benzodiazepine antagonist, has been used to reverse sedation in a double-blind, controlled study of patients undergoing upper gastrointestinal (GI) endoscopy. Forty patients in each of two centres were given a standard dose of either flumazenil (n = 40) or placebo (n = 40) after gastroscopy under midazolam sedation. Assessments were made of degree of sedation, psychomotor ability and amnesia up to 24 h after endoscopy. In patients treated with flumazenil, sedation was effectively reversed within 5 min in 77.5% of cases compared to 27.5% of patients treated with placebo. The difference was both clinically and statistically significant at 5 and 30 min but not at 60 min after reversal. There was no evidence of resedation 18 to 24 h later. Times to complete Trieger dot-joining tests were significantly faster in the flumazenil group at 5, 30 and 60 min. Amnesia for the procedure was retained but did not occur for events after administration of flumazenil. The only adverse event was severe pain in the arm of one patient during the injection of flumazenil. Flumazenil rapidly and safely reverses midazolam-induced sedation while retaining amnesia for gastroscopy.