Spectrin levels in erythrocytes have been related to several biomechanical and biophysical membrane properties essential to the survival and function of the cell. Populations of erythrocytes display a natural and finite range of sensitivities to osmotic shock that has been directly correlated, in studies from other laboratories, to the presence of spectrin. We used a procedure to isolate subpopulations of 1) the osmotically most sensitive and 2) the osmotically most resistant erythrocyte membranes in an attempt to select for membranes enriched and depleted in spectrin (and/or a related component). The mechanical function of the spectrin-based membrane skeleton was further explored in these two subpopulations by searching for any effect on the time-dependent increase in fusion zone diameter in pairs of electrofused erythrocyte ghosts as a model for cell fusion. The results clearly show that the diameter expansions in fusions of membranes from osmotically resistant erythrocytes are faster in the early stage (up to 9 to 10 s after fusion) but do not thereafter expand as far as in fusions of membranes from osmotically sensitive membranes.