The usefulness of intravenous dexmedetomidine infusion for maintenance of anesthesia was studied in patients anesthetized with thiopental, fentanyl, nitrous oxide, and oxygen. Isoflurane was added as needed. The study was conducted in two parts, the first of which was an open dose-response study that comprised 14 women undergoing abdominal hysterectomy. After a suitable infusion regimen of dexmedetomidine was determined according to hemodynamic criteria, 20 patients were included in a double-blind, randomized placebo-controlled trial (10 receiving dexmedetomidine, 10 saline solution). Dexmedetomidine was administered as a two-step infusion to rapidly achieve a steady-state plasma concentration. The infusion was started with an initial dose given over 10 min before the induction of anesthesia; at induction the maintenance rate was begun and continued until closure of the abdominal fascia. The infusion regimens of dexmedetomidine tested in the dose-response study ranged from 120 ng.kg-1 x min-1, followed by 6 ng.kg-1 x min-1, to 270 + 13.5 ng.kg-1 x min-1. In the second part of the study, an initial infusion of 170 ng.kg-1 x min-1 was chosen, followed by 10 ng.kg-1 x min-1 for maintenance. Anesthesia was induced with thiopental (4.0 mg/kg) and maintained with isoflurane in 70% nitrous oxide and oxygen. Isoflurane was administered according to predetermined hemodynamic criteria. Dexmedetomidine infusion did not completely abolish the need for isoflurane but diminished its requirement by > 90% (P = 0.02). The heart rate response to endotracheal intubation was significantly blunted.