SUMMARY The purpose of the present study was to investigate erythrocyte membrane abnormalities in hypertension by means of an electron spin resonance and spin-label technique. The erythrocytes from spontaneously hypertensive rats (SHR) and humans with untreated essential hypertension were examined and compared with their normotensive counterparts, and electron spin resonance spectra were obtained for a fatty spin-label agent (5-nitroxy stearate) incorporated into the erythrocyte membranes. The value of outer hyperfine splitting (2T\) was significantly higher in erythrocytes of SHR and humans with essential hypertension than in erythrocytes of normotensive controls (at 37 °C: SHR, 56.14 ± 0.51 gauss [G], n = 8; Wistar-Kyoto rats, 52.22 ±0.86 G, n = 4, p<0.01; humans with essential hypertension, 56.94 ± 0.27 G, n = 11; normotensive subjects, 55.44 ± 0.36 G, n = 8, p<0.01). The order parameter (5) was also increased in the hypertensive rats and humans compared to their respective normotensive controls. When calcium was loaded to erythrocytes with calcium ionophore A23187 (0.9 fiM) and CaCl 2 (1.0 mM), the parameters of the spectra were increased. These changes were more prominent in the hypertensive groups than in the normotensive controls. These results revealed that the erythrocyte membranes of the hypertensive subjects tolerated different spin motions than those of the normotensive controls in the electron spin resonance study and that membrane fluidity might be decreased in hypertension. Additionally, calcium loading to erythrocytes caused the reduction of membrane fluidity. Therefore, it is suggested that an abnormality of calcium handling at the cellular level might affect physical properties of the biomembranes in hypertension. 1 " 5 It seems likely that generalized abnormalities of the membranes could be involved not only in vascular smooth muscle cells but also in circulating blood cells. Erythrocytes are widely studied because they are a