The pharmacokinetics of morphine have not been previously studied in children following cardiac surgery for tetralogy of Fallot (TOF) or transposition of the great arteries (TGA). Morphine steady-state pharmacokinetics were studied in 21 children undergoing repair of TOF, TGA, or atrio-ventricular septal defects (AVSD). Children with TOF or TGA had increased right-sided pressures with no differences between the groups. Children with TOF had significantly faster clearance rates of morphine (1.39 +/- 0.37 L/kg/h) than children following the Fontan procedure (0.86 +/- 0.31 L/kg/h, P < 0.01). When stratifying children by their postsurgical needs for inotropic support, those needing epinephrine, dopamine, or dobutamine at more than 10 micrograms/kg/min had significantly slower clearance rates (0.73 +/- 0.3 L/kg/h) when compared to the rest of the patients (1.5 +/- 0.41 L/kg/h, P < 0.05). Because most children needing inotropic support underwent the Fontan procedure, it is conceivable that their cardiovascular status had a major impact on morphine metabolism. These results suggest a 50% reduction in morphine dosage in children requiring inotropic support following cardiac surgery.