Cardiovascular and respiratory effects of pediatric preanesthetic premedication have received only minimal attention, probably because most children tolerate such drugs without apparent ill effect. In children with congenital heart disease or other serious illness, there is often reluctance to use premedication. We sought to determine whether different premedication regimens produced significant cardiorespiratory effect. A randomized prospective study of the cardiovascular and respiratory effects of different oral, nasal, and rectal premedication regimens was conducted. Fifty-eight young children (average age 2.7 yr) were studied. Oral meperidine (3 mg/kg) with pentobarbital (4 mg/kg) decreased heart rate, mean arterial pressure, cardiac index, respiratory rate, and oxygen saturation. Stroke volume was maintained. Nasal ketamine (5 mg/kg) with midazolam (0.2 mg/kg) produced no significant cardiovascular or respiratory effects. Rectal methohexital (30 mg/kg) increased heart rate with a coincident decrease in stroke volume but had no other positive or negative cardiac or respiratory effect. This information documents disparate cardiorespiratory effects of different preanesthetic medications in normal children.