The occurrence of subaortic stenosis (SAS) has been associated with congenital defects and morphologic abnormalities such as ventricular septal defect (VSD) and unusually steep aorto-septal angle (AoSA). Altered flow fields due to these abnormalities have led to the hypothesis that a fluid dynamic mechanism may contribute to the formation of SAS. Previously we have shown that the peak shear stress on the septal wall increases as AoSA becomes more acute. The strong, but incomplete, association of VSD with SAS suggests that its effect on the left ventricular flow field may interact with the AoSA to modulate septal shear stress. Methods: We tested this concept using a previously developed fluid dynamic model implemented on a Cray supercomputer. Shunt velocities ranged from 1-5 m/s, aortic velocities from 0.5-1 m/s, AoSA from 120-150 degrees, and VSD diameters from 3-6 mm. The position of the VSD was varied from 2-10 mm from the aortic valve. These ranges were based on echocardiographic measurements of patients in our population. Results: Acute AoSA caused increases in septal shear stress. The extent of increase was controlled by VSD position. For a baseline case of a 3 mm VSD, varying the AoSA from 150 to 120 degrees produced a 45% increase in septal shear stress. Moving the VSD in the direction of the aortic valve produced additional significant increases in septal shear stress (e.g., 17% for 4 mm distance). Conclusions: The complex interaction between VSD and AoSA in affecting septal fluid dynamics may explain why SAS is strongly associated with VSDs, but not all patients with VSDs develop SAS. Specifically, the position and severity of the VSD control stress effects caused by AoSA and may be critical in determining which patients are at risk for developing SAS.