The factors which give rise to the normal relationship between the great arteries and their respective ventricles are unknown. The developmental anatomy of this region was studied by using frontal, sagittal, or transverse serial histologic sections of 17 normal human embryos of Carnegie stages 15-19 from the Carnegie Embryological Collection. Distances and angles between major anatomic landmarks were determined by using computer reconstructions of the serially sectioned embryos, three-dimensional analytic geometry, and Euclidean distance formulas. The findings show that between stages 15 and 19 there is a marked rotation of the axis of the semilunar valves: frontal 121 degrees counterclockwise, sagittal 196 degrees counterclockwise, and transverse 240 degrees clockwise. Simultaneously the great arteries lengthen at a faster rate than the rest of the heart; and there is also an increase in the caliber and wall thickness of the great arteries. These results suggest that the changing rate of growth between the great arteries and the heart is necessary to align the great arteries, the semilunar valves, and the muscular outflow tract septum appropriately with respect to the interventricular septum. Reductions in the rate of growth of the great arteries relative to the heart could, by causing changes in the rotation of great arteries and outflow tract septum, have a role in the pathogenesis of cardiovascular malformations such as tetralogy of Fallot and transposition of the great arteries.