Ninety women undergoing gynecologic laparoscopy were randomly given clonidine 3 or 4.5 μg/kg or saline intramuscularly 45–60 min prior to induction of anesthesia. Anesthesia was induced with thiopental 3.5 mg/kg and maintained with 0.3% end-tidal isoflurane in nitrous oxide and oxygen. The laparoscopy did not begin sooner than 20 min after tracheal intubation. Arterial blood pressure and heart rate were monitored with an automatic oscillometer. When compared with the baseline values, clonidine 4.5 μg/kg significantly (P< 0.001) decreased the mean arterial pressure (MAP) measured before induction of anesthesia. In all three groups, blood pressure and heart rate increased after tracheal intubation and after beginning of laparoscopy (P< 0.001), but the increments were significantly greater in the control group than in the study groups. During anesthesia alone without surgical stimulation, and again in the recovery room, MAP and heart rate were lower in the study groups than in the control group. Plasma β-endorphin immunoreactivity (ir β-E) was measured for ten control-group women and ten women receiving clonidine 4.5 μg/kg before premedication, before and after induction of anesthesia, during laparoscopy, and 1 h after the procedure. The plasma ir β-E increased significantly after the beginning of laparoscopy in both the control group and those given clonidine, but the increase was significantly less (P< 0.05) in the women premedicated with clonidine. The blunting effect of clonidine on hemodynamics and plasma β endorphin may reflect a deeper level of anesthesia in those women receiving clonidine as preanesthetic medication or can be explained by an interaction of clonidine with endogenous opiates. The authors conclude that intramuscularly administered clonidine premedication effectively prevents the maximal hemodynamic responses to tracheal intubation and to gynecologic laparoscopy. Further clinical studies on the clinical importance of the role of clonidine preanesthetic medication are warranted.