It has been shown that rheological abnormality might be an etiological factor in hypertension, Recent studies have revealed that human erythrocytes possess a nitric oxide (NO) synthase and that this activation might be involved in the regulation of rheological properties of erythrocytes. The present study was undertaken to investigate the role of NO in the regulation of membrane functions of erythrocytes in patients with essential hypertension by means of an electron paramagnetic resonance (EPR) and spin-labeling method. The NO donor S-nitroso-N-acetylpenicillamine (SNAP) decreased the order parameter (S) for 5-nitroxide stearate (5-NS) and the peak height ratio (h(0)/h(-1)) for 16-NS obtained from EPR spectra of erythrocyte membranes in a dose-dependent manner, The finding indicated that the NO donor increased the membrane fluidity of erythrocytes, In addition, the effect of SNAP was significantly potentiated by 8-bromo-cyclic guanosine monophosphate, By contrast, the change of the fluidity induced by SNAP was reversed in the presence of L-N-G-aitroarginine methyl ester and asymmetric dimethyl L-arginine, In patients with essential hypertension, the membrane fluidity of erythrocytes was significantly lower than in the normotensive subjects, The effect of SNAP was more pronounced in essential hypertension than in normotensive subjects. These results showed that NO increased the membrane fluidity and decreased the rigidity of cell membranes. Furthermore, the greater effect of NO on the fluidity in essential hypertension suggests that NO might actively participate in the regulation of rheological behavior of erythrocytes and have a crucial role in the improvement of microcirculation in hypertension.