Fourteen patients with essential hypertension (blood pressure 167 ± 2 106 ± 2 [ mean ± standard error of the mean] mm Hg ) were studied prospectively to determine the pathophysiologic correlates of their “stress” or relative polycythemia. All patients had a high hematocrit level (53.1 ± 0.4 vol percent), contracted plasma volume (16.2 ± 0.4 ml/cm height) and normal red cell mass and serum erythropoietin levels. Blood and plasma viscosity (0.076 ± 0.005 and 0.017 ± 0.001 poise, respectively) were increased, and plasma renin activity in the supine, resting state averaged 1.8 ± 0.3 ng/ml per hour. All patients were treated with methyldopa to achieve normal arterial pressure and the previous determinations were repeated after 1 and 4 weeks of treatment. Reduction of pressure was associated with expansion of plasma volume ( P < 0.001) and significant decreases in hematocrit, blood and plasma viscosity and resting plasma renin activity ( P < 0.001). Red cell mass and serum erythropoietin levels remained unchanged. Therefore, the so-called stress polycythemia is a pathophysiologic manifestation of the hypertensive vascular disease in which the abnormal hemodynamic and rheologic alterations can be reversed by antihypertensive therapy. The significance of this reversal may have some bearing upon the high prevalence rates of severe cardiovascular complications associated with so-called stress polycythemia and high renin essential hypertension.