BACKGROUND: In vivo experimentation is the most realistic approach for exploring the vascular biological response to the hemodynamic stresses that are present in life. Post-mortem vascular casting has been used to define the in vivo geometry for hemodynamic simulation; however, this procedure damages or destroys the tissue and cells on which biological assays are to be performed. METHOD OF APPROACH: Two statistical approaches, regional (RSH) and linear (LSH) statistical hemodynamics, are proposed and illustrated, in which flow simulations from one series of experiments are used to define a best estimate of the hemodynamic environment in a second series. As an illustration of the technique, RSH is used to compare the gene expression profiles of regions of the proximal external iliac arteries of swine exposed to different levels of time-average shear stress. RESULTS: The results indicate that higher shears promote a more atheroprotective expression phenotype in porcine arterial endothelium. CONCLUSION: Statistical hemodynamics provides a realistic estimate of the hemodynamic stress on vascular tissue that can be correlated against biological response.