We present a series of three children with trisomy 21 and obstructive sleep apnea who required sedation during magnetic resonance imaging of the upper airway. In an effort to provide effective sedation with limited effects on cardiovascular and ventilatory function, sedation was provided by a combination of ketamine and dexmedetomidine. Sedation was initiated with a bolus dose of ketamine (1 mg x kg(-1)) and dexmedetomidine (1 microg x kg(-1)) and maintained by a continuous infusion of dexmedetomidine (1 microg x kg(-1) x h(-1)). One patient required a repeat of the bolus doses of ketamine and dexmedetomidine and an increase of the dexmedetomidine infusion to 2 microg x kg(-1) x h(-1). Effective sedation was provided for all three patients. We noted no clinically significant hemodynamic or respiratory effects. No central apnea was noted although there was a brief episode of upper airway obstruction in one patient which responded to repositioning of the airway. All three patients developed some degree of hypercarbia with maximum P(E)(CO2) values of 6.4, 6.9, and 6.8 kPa (49, 53, and 52 mmHg), respectively. To date, this is the first report regarding the use of this combination in pediatric patients. Given the preliminary success noted in our three patients, prospective trials evaluating the efficacy of a dexmedetomidine-ketamine combination appears warranted.