Summary Red blood cell populations separated by density centrifugation were compared in a dynamic assay of osmotic stress. Red blood cells from Beagles genotypically normal and nonanemic (nonaffected), Beagles with inherited hemolytic anemia (anemic), and Beagles presumed to be carriers of the anemia trait (trait carriers) were examined for rate and extent of swelling after exposure to the ionophore A23187 in a medium containing calcium and potassium chloride. Comparisons were made between rbc populations separated on the basis of density. Significant differences were observed in the rates of cell swelling in rbc populations separated by density between nonaffected and anemic Beagles. The response of rbc from Beagles presumed to carry the anemia trait was similar to that of rbc from nonaffected dogs. One phenotypic expression of this inherited abnormality of rbc in Beagles was an accelerated rate of rbc swelling under osmotic stress, and this swelling response diminished with increasing rbc density.