A kinetic method for detecting changes in red blood cell shape with time re
solution on the order of seconds is described. The definition of shape inde
x (SI) and the experimental conditions under which the measurements should
be conducted are given, and the relationship between SI and morphological i
ndex, which is often used to quantitatively assess red blood cell morpholog
y, is established. Further, we show that the method can be used to assess s
hape changes under a variety of experimental conditions known to cause majo
r perturbations in the morphology of red blood cells (such as addition of l
ysolecithin or chlorpromazine) and to detect changes in shape during chemic
al fixation for observation with microscopy. We report here that the abilit
y of glutaraldehyde to fix red blood cells without additional alteration in
shape strongly depends on the morphology that is being fixed and the initi
al state of the cells.