In 11 untreated patients with essential hypertension, the hemodynamic responses to antihypertensive therapy with prazosin were evaluated in terms of associated changes in blood viscosity (ηB). At high and low blood flow velocities, changes in ηB were correlated (r = 0.63–0.708, p < 0.05) with changes in systolic blood pressure. Changes in ηB and diastolic blood pressure were significantly correlated (r = 0.684–0.723, p < 0.05 or better) only at higher blood flow conditions. Plasma protein concentration and hematocrit changes were similar in magnitude, and both were correlated (r = 0.759, p < 0.01) with blood pressure changes. During prazosin therapy, reciprocal changes in fibrinogen and globulin concentrations (r = −0.605, p < 0.05) accounted for the constant plasma viscosity (ηB) and degree of red cell aggregation in untreated and treated patients. These studies suggest that the extent to which total peripheral resistance and, hence, diastolic blood pressure, fall during prazosin therapy is associated with preferential decrease in ηB in higher-flow resistance vessels, while in the low-flow capacitance system, changes in viscous flow resistance and diastolic blood pressure are not generally correlated. Furthermore, the inverse relationship between fibrinogen and globulin concentrations indicates that decreased ηp does not necessarily accompany hemodilution. Plasma renin activity, creatinine clearance, and daily urinary excretion of sodium, potassium, and aldosterone were similar before and during prazosin therapy. Significant correlations between changes in these variables and blood pressure were not generally observed. Thus, reductions in arterial pressure during prazosin therapy are accompanied by proportional decreases in ηB at high flow velocities. Consequently, microcirculatory blood flow and organ perfusion are well maintained.