A study of ventricular septal defects (VSD) is made in relation to anomalies of the conotruncus and aortic arch. One hundred-nineteen autopsy cases were examined. These included 66 of VSD and 53 of aortic arch anomalies. Within the group of aortic arch anomalies, 14 cases of interrupted aortic arch are tabulated. Five cases bearing on the question of transformation of VSD to tetralogy of Fallot are presented. A further case is presented, demonstrating the heretofore undescribed combination of tetralogy of Fallot with interrupted aortic arch. The VSD is discussed in terms of the developmental concept of a ventricular flow pathway. It is emphasized that the defect is not the primary cause of the conotruncal or aortic arch malformation. The study suggests that the natural history of the VSD may include transformation to the tetralogy of Fallot via Eisenmenger's syndrome.