BACKGROUND: This study was designed to determine the efficacy of a combined use of oral clonidine and intravenous esmolol for blunting the sympathetic response during tracheal intubation. METHODS: Forty-eight patients for hysterectomy were randomly divided into four groups: placebo A and B in Group I (n = 12), placebo A and esmolol (1.0 mg/kg) in Group II (n = 12), clonidine (4 microgram/kg) and placebo B in Group III (n = 12), and clonidine (2 microgram/kg) and esmolol (0.5 mg/kg) in Group IV (n = 12) were administered respectively. Premedication with oral clonidine or placebo A at 90 minutes before induction and intravenous esmolol or placebo B just prior to induction were given. Patients were induced with thiopental and ventilated with N2O-O2-enflurane (1.5 vol%). Vecuronium was given immediately after administration of thiopental for tracheal intubation. BP and HR were recorded at the resting state before premedication (control), at 1 min before induction (T - 1), immediately after intubation (T + 0), 3 min and 5 min after intubation (T + 3 and T + 5), and were converted into a percentage (%) of the control value (Vcontrol). RESULTS: SBP increased in Group I (T + 0 and T + 3) and decreased in Group III (T + 5) compared with Vcontrol (P < 0.05). HR increased in Group I (T + 0 and T + 3) and Group III (T + 0) compared with Vcontrol (P < 0.05). SBP% of Vcontrol in Groups II, III and IV (T + 0 and T + 3) were lower than that of Group I (P < 0.05). HR% of Vcontrol in Group II and IV (T + 0, T + 3 and T + 5) were lower than those of Groups I and III (P < 0.05). There were one episode of hypotension in Group II at 5 min after intubation and two cases of intraoperative hypotension in Group III. CONCLUSIONS: Combined administration of oral clonidine and intravenous esmolol was effective in attenuating the increase of BP and HR during tracheal intubation without any side effects. This combined method would be an effective method when dose-related side effects of each drug limit their use.