SummaryDown's syndrome is commonly associated with cardiac malformations and sleep related upper airway obstruction. The dose response for ketamine in the presence of an infusion of fentanyl was determined in 28 consecutive children (3–51 months) with Down's syndrome and congenital heart disease during haemodynamic catheterization. The children were premedicated with flunitrazepam orally and glycopyrrolate i.v. Ventilation was continuously monitored with a capnograph. Fentanyl 1 μg·kg−1and 1 μg·kg−1·h−1was administered in fixed doses for induction and maintenance of sedation, respectively. The mean induction and maintenance requirements of ketamine were 1.5 ± 0.5 mg·kg−1and 1.8 ± 0.8 mg·kg−1·h−1, respectively. In infants younger than 6 months, more ketamine was needed for both induction and maintenance than in older children (P<0.005). Normoventilation without any airway manipulation could be maintained in 15 patients (54%). Respiratory difficulties were frequent: hypoventilation required temporary mask ventilation, insertion of a nasopharyngeal tube or tracheal intubation in two, seven and four children, respectively. Oral flunitrazepam premedication and intravenous sedation with low‐dose fentanyl and ketamine combined with close monitoring of ventilation can be used for cardiac catheterization in children with Down's syndrome. However, the described combination of sedative drugs does not prevent the occurrence of sleep related