The goad of this study was to determine whether the elevated flux of sodium and potassium through the erythrocyte membrane of spontaneously hypertensive rats (SHR) is due to an intrinsic difference in the cell membrane or to a humoral factor present in the plasma. Isolated and washed erythrocytes from SHR and normotensive Wistar Kyoto (WKy) and Sprague-Dawley (SD) rats, were incubated in 1) a physiological salt solution, 2) WKy or SD plasma and 3) SHR plasma. Incubations were performed at 4°C for 23 h. Erythrocytes from SHR incubated in physiological salt solution had significantly greater Na + and K + fluxes than those from normotensive WKy and SD rats ( P <0.005). Plasma from any of the three strains of rats, as compared to physiological salt solution, increased Na + influx in the following order: SD>WKy>SHR. Erythrocyte K + efflux was not altered by plasma. We conclude that the elevated flux of Na + and K + in SHR erythrocytes is due to an intrinsic difference in the cell membrane. The greater Na + influx in plasma from any strain of rats is not correlated with the blood pressure of the rat. The lesser increase in Na + influx in crythrocytes incubated in plasma from SHR masks the greater intrinsic membrane permeability in the SHR erythrocyte when Na + fluxes are studied in whole blood. The elevated flux of Na + and K + through the erythrocyte membrane of SHR may reflect a general membrane defect that underlies the pathogenesis of elevated arterial pressure.