The viscosity of a suspension of 45 per cent human erythrocytes in Ringer-albumin solution at 37 C was determined. Local anesthetics (hydrochloric salts of lidocaine, etidocaine, prilocaine, mepivacaine, bupivacaine, procaine, and tetracaine) were added to the erythrocyte suspension. In the presence of local anesthetics, the viscosity of the erythrocyte suspension at high shear rates was essentially constant. At low shear rates less than 5 sec-1), the viscosity increased progressively as the anesthetic concentration was increased. Erythrocytes in the suspension were transformed progressively from discoid to cup-shaped as the concentration of anesthetic agent was increased. The transformation into the cup shape in the presence of local anesthetics may be attributed to the preferential expansion of surface area and increase in surface tension in the inner half-layer of the erythrocytic membrane. These morphologic changes of erythrocytes corresponded in general to the increase in viscosity of erythrocyte suspensions. The morphologic and viscosity changes were reversible by rewashing. The relative effectiveness of the anesthetic agents used, as estimated from the concentrations needed to increase viscosity at a shear rate of 0.5 sec-1by 20 per cent, can be correlated with their relative intrinsic potencies, determined from isolated-nerve preparations. These data suggest that alterations in rheologic characteristics of erythrocyte suspension may be a useful index for the assessment of relative potencies of local anesthetics. The results further suggest that the inner half-layer of the membrane is the site of action for all the local anesthetics studied.