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Clonidine's antihypertensive effects result from the activation of central α2-adrenergic receptors. This results in a decrease in sympathetic or vasomotor tone from the medulla and a decrease in heart rate and systemic vascular resistance. Despite reports of its use in the pediatric population as a premedicant for the operating room, as an adjunct to caudal epidural anesthesia, to supplement opioid analgesia, and to treat behavioral disorders, there is limited experience with its use as an antihypertensive agent in children. The author describes his experience with clonidine to control mean arterial pressure in three pediatric neurosurgical patients when other options for oral therapy including angiotensin converting enzyme (ACE) inhibitors, β-adrenergic antagonists, and calcium channel antagonists proved to be ineffective. Previous experience with clonidine as an antihypertensive agent in children is reviewed and recommendations made concerning possible dosing regimens.