An altered state of cell hydration is a hallmark of a number of RBC disorders. The two parameters most often used to characterize the state of cell hydration are (a) the complete cell density distribution profile, and (b) the fraction of cells with densities greater than a defined value. Buoyant density cell fractionation with a variety of polymers has long been the preferred method for obtaining data on cell density distribution. Although this method provides accurate and quantitative information on the state of RBC hydration, its applicability has been limited due to the time-consuming experimental procedure involved in generating the data. A recently developed light- scattering method has been used in the present study to quantitate RBC density distribution. This new method accurately quantitates both the cell density distribution profile and the fraction of dense, dehydrated cells in various RBC disorders. The ability of the automated method to generate this information rapidly makes possible objective testing of different hypotheses concerning the contributions of cell hydration and dehydration to the pathophysiology of various RBC disorders.