A series of studies have been undertaken correlating sodium intake, blood pressure and red cell 22Na efflux. The results for male and female patients differ. In male patients with elevated blood pressure, increased sodium intake caused a rise in blood pressure and a fall in red cell 22Na efflux rate. In female patients the results were variable and while certain females followed the above pattern, others had the converse response. Evidence is presented that the change in red cell 22Na efflux is due to a factor in plasma that inhibits the ouabain sensitive component of sodium efflux. This increases after acute and chronic sodium loading and may be similar to natriuretic factor described previously. It is postulated that increased sodium intake causes hypertension by producing a humoral factor that inhibits sodium transport out of cells and that this alters the calcium content of muscle cells and increases their contractility and thus produces hypertension.