This study was performed to investigate the membrane fluidity of hypertension by means of an electron spin resonance (E.S.R.) and a spin-labeling technique. Erythrocytes from patients with untreated essential hypertension (WHO I, II) and secondary hypertension were compared with those from normotensive subjects, and E.S.R. spectra for a fatty acid spin label agent (5-nitroxy stearate) incorporated into the erythrocyte membranes were obtained. The values of outer hyperfine splitting (2T'parallel) and order parameter (S) were significantly higher in erythrocytes from patients with essential hypertension than in those from normotensive subjects. However, these values were not significantly changed in patients with secondary hypertension compared with those in the normotensive subjects. This finding may indicate the reduced erythrocyte membrane fluidity in essential hypertension. Calcium-loading to erythrocytes with calcium-ionophore caused a greater decrease in the membrane fluidity of erythrocytes in patients with essential hypertension than in those from the normotensive subjects. This Ca-induced change in membrane fluidity was inversely correlated with plasma renin activity in essential hypertension. In addition, changes in membrane fluidity by Ca-loading in essential hypertension were inhibited by Ca-antagonists (diltiazem, verapamil). These results demonstrate that the membrane fluidity of erythrocytes might be decreased in essential hypertension, and that this abnormality could be accelerated by calcium, especially in low renin essential hypertension. Furthermore, it is suggested that Ca-antagonists might correct this Ca-abnormality at cellular levels of hypertension.