In 20 patients with coma (grade 4: n = 7, grade 3: n = 8, grade 2: n = 2, grade 1: n = 3) due to benzodiazepine intoxication, solely or combined with alcohol or other psychoactive drugs, the effect of a specific benzodiazepine antagonist, Flumazenil (Ro 15-1788), was evaluated. In terms of coma depth, 80% of the patients responded to application of 1.96 mg Flumazenil as a mean with immediate awakening or improvement of at least two steps in coma grading. In those 3 patients, who failed to respond to Flumazenil, the history revealed amitriptyline or barbiturates to be responsible for the comatose state. The observed side-effects of Flumazenil included increase (n = 4) or decrease (n = 3) of blood pressure, increase of heart rate (n = 7), cutaneous flush (n = 1) and ventricular extrasystoles (n = 1). Agitation and generalized convulsions, each observed in 1 patient, presumably were due to an acute benzodiazepine-withdrawal rather than an intrinsic side effect of the antagonist. In conclusion, Flumazenil proved to be a potent antagonist of benzodiazepines in patients with severe coma and even may serve as a valuable diagnostic in cases of suspected benzodiazepine intoxication.