Whole cell deformability of red cells was measured as a continuous function of suspending medium osmolality using the ektacytometer, a laser-diffraction viscometer. Study of normal cells in which water content and membrane surface area had been selectively modified showed that this technique can detect changes in these properties with high sensitivity. The osmotic deformability profiles obtained from this assay provide information about cell water content, surface area, and the heterogeneity in these cellular properties, information that by conventional methods would require several different types of measurements. Application of this approach to a variety of pathologic blood samples showed that various hematologic disorders can be characterized by the shape of this profile and the position of specific features of the profile along the osmolality axis. Measurement of osmotic deformability profiles thus provides a convenient and comprehensive means of identifying abnormalities either in red cell water content or surface area.