The membrane proteins of normal and hereditary spherocytosis have been labelled with a maleimide-analog nitroxide spin label and studied by electron paramagnetic resonance techniques. The spectral amplitude ratios from weakly and strongly immobilized labels differed slightly at 20° and 40°. Increasing the temperature to 47° and incubating for long time periods markedly accentuated the difference. It is suggested that the apparent differences in heat sensitivity between normal and hereditary spherocytosis erythrocyte membrane proteins reflect a latent structural alteration(s) of hereditary spherocytosis erythrocyte membrane proteins. Such structural alterations may result in altered functional behavior when the membrane is subjected to stress.