Preoperative balloon atrial septostomy is the standard therapy for babies with uncomplicated cyanotic dextrotransposition of the great arteries despite the effectiveness of prostaglandin E1 infusion in alleviating systemic hypoxemia and the reported success of arterial switch repair during the 1st weeks after birth. The clinical records and echocardiographic findings of 23 infants (mean birth weight +/- SD 3.3 +/- 0.5 kg) with uncomplicated transposition of the great arteries were analyzed. Fifteen infants (Group I) did not undergo septostomy, and 8 (Group II) underwent septostomy. Before prostaglandin infusion, mean arterial oxygen tension (Po2) in Group I (26 mm Hg) did not differ from that in Group II. After prostaglandin infusion, Po2 increased significantly in Group I (43 +/- 8 mm Hg, p less than 0.001) but not in Group II despite a widely patent ductus and predominant left to right ductal shunt in all. After septostomy, Po2 increased significantly (43 +/- 4 mm Hg, p less than 0.03), and did not differ from that in Group I. Echocardiographic features generally demonstrated a nonrestrictive foramen ovale in Group I and a restrictive foramen ovale in Group II. The latter was associated with persistent hypoxemia after prostaglandin. Thus, the diameter of the foramen ovale was the primary factor influencing arterial oxygenation during prostaglandin infusion. Babies underwent the arterial switch operation at a mean age of 70 +/- 65 h with an overall survival rate of 96%; there was only one postoperative death (Group II). Absence of septostomy had no negative influence on any postoperative variable, including duration of ventilatory and inotropic support, time to discharge, or mortality.(ABSTRACT TRUNCATED AT 250 WORDS)