BACKGROUND Clonidine, an α-2 adrenergic agonist, is used in the perioperative period and in intensive care for the management of hypertension. The in vivo and in vitro effects of clonidine on the actions of nondepolarizing neuromuscular blocking drugs are conflicting. We evaluated the potency and time course of rocuronium-induced neuromuscular block after prolonged pretreatment with clonidine in rabbits. METHODS Sixty rabbits were randomly assigned to three groups; control (C) group: normal saline 0.1 ml/kg daily subcutaneous for 6 weeks; S3 group: clonidine 4 µg/kg daily subcutaneous for 3 weeks; S6 group: clonidine 4 µg/kg daily subcutaneous for 6 weeks. The dose-response relations of rocuronium were tested in 30 rabbits (10 from each of the three groups) during ketamine-thiopental anesthesia, while the time course of rocuronium 0.6 mg/kg was examined in 10 rabbits each from the three groups. RESULTS There was no difference in mean arterial pressure and pulse rate among the experimental groups. The calculated ED(50) for rocuronium decreased significantly from 64.1 µg/kg (C group) to 50.3 µg/kg (S3 group) and 47.8µg/kg (S6 group) (P < 0.001). There was no difference in the onset and the recovery times after rocuronium. CONCLUSIONS Rocuronium after pretreatment with clonidine for three or six weeks may have an increased effect, but no difference in the duration of action compared with control group.