Background and Purpose-Patients who have sustained a neurological injury and then improved may experience transient reemergence of their syndromes when given benzodiazepines. As a step toward assessing whether neurotransmitter systems underlie poststroke clinical improvement, we selected midazolam, a γ-aminobutyric acidA (GABAA) agonist, for systemic administration to measure general or stroke-specific effects in patients. Methods-Eight patients with image-verified stroke (5 with left-sided and 3 with right-sided cerebral lesions) participated. The strokes had occurred from 7 days to 6 years earlier, with patients showing clinical improvement from their initial syndromes. Each patient underwent baseline testing for motor function, aphasia, and left hemispatial neglect, after which intravenous midazolam was delivered until mild drowsiness was detected. Patients were tested during this period and again after 2 hours when sedation had dissipated. Results-After the administration of midazolam, the 5 patients with left hemisphere stroke demonstrated reemergence or worsening of their initial right hemiparesis and aphasia but showed no left neglect. The 3 patients with right cerebral stroke showed reemergence of left hemiparesis and left visual field neglect but no aphasia. All patients returned to baseline after 2 hours. Conclusions-Under conditions of light sedation, patients whose initial stroke syndrome had substantially improved clinically showed transient reemergence of their initial focal syndrome. These data suggest a possible role for GABAA-mediated neurochemical mechanisms in poststroke improvement and sensitivity to medication effects.