Our data show that the ESR spectrum of 5-nitroxide stearate bound to erythrocyte membranes varies with the amount of label bound and suggest that, at high binding, a significant proportion of label molecules lie within approximately equal to 15-10--8 cm; this gives rise to spin-exchange (ambient temperature) and dipole-dipole interactions. We find that these spectral manifestations due to label clustering can be abolished by reduction of pH and the conjoint action of lysolecithin and trypsin, although both perturbations increase 5-nitroxide stearate binding. Both perturbations are known to mobilize intramembranous particles by modifying or extracting some membrane proteins. We accordingly suggest that the lipids and proteins of erythrocyte membranes exist in a relatively fixed mosaic, and that the mobility of both components is restricted by some membrane-associated protein framework.