von Willebrand factor (vWF) was analyzed by electron microscopic and quasi-elastic light scattering techniques in order to evaluate the size and shape of this heterogeneous polymeric plasma glycoprotein. Electron micrographs demonstrated that native vWF molecules are flexible, linear polymers, ranging in contour length from 100 to 1300 nm. In their typical configuration, the polymers were coiled upon themselves with maximal diameters ranging from 60 to 200 nm. Individual repeating protomeric subunits were discernible in occasionally noted, uncoiled polymers and measured 100 nm X 1.5-2.0 nm. Quasi-elastic light scattering analysis confirmed that measurements of the size and shape of purified vWF molecules in solution were similar to those obtained with electron microscopic techniques. In addition, the mean Stokes radius and mean radius of gyration assessed by quasielastic light scattering were directly related over a wide range of values, as were the diameter and contour length measured from electron micrographs, suggesting that the overall shape of polymers does not change with increasing size. This study supports the concept that native vWF molecules are flexible, linear polymers. In addition, this study clearly shows that the polymer configuration assessed from electron micrographs is a valid representation of the configuration of the polymer in solution. The data presented also provide the first evidence for a well-defined, repeating protomeric subunit.