In the past, red cell resting shape could only be assessed by subjective scaling, red cell deformability by a variety of rheological tests that are extremelydifficult to standardize and which all subject the RBC to high deforming forces. None of the latter have been accepted as reference in haematology, haemorheologyor pharmacology. A recent development from our group now allows objective, numerical analysis of red cell membrane curvature (i.e. the echinocytic or stomatocytic deviation from the discocytic resting shape) by a tangent count procedure in optical sections through freely suspended, randomly oriented RBC: (Grebe et al. Biorheology 22(6), 1985). Also, the deformation of point attached erythrocytes under the influence of extremely low shear stresses (0.05 Pa to 0.5 Pa, ARTOANN:Clin. Hemorheology 6, 1986), which are at least two orders of magnitude lower thanthat in any routinely available filtration method allows for the first time to model in vitro the extreme low flow states that occur in severe forms of haemodynamic insufficiency. These two methods in combination are ideally suited for routine tests of drug effects on normal human RBC: the drug action on RS can be monitored continuously during the action of drugs in the suspending medium; likewise, RISA can be recorded automatically on one population of adherent RBC while altering the composition and the drug concentration in the superfusate. The two methods were applied in combination to test rheological and membranological effects of two distinctly different compounds, namely Bencyclan (Bencylan-Hydrogen-Fumarate) and Vinpocitin (Aethyl vincamin) in normal cells and in cells after exposure to "stress conditions", i.e. hyperosmolarity and lactacidosis. Both olrugs given to n o r m a 1 RBC produce stomatocytosis in a done dependent fashion (1-100 uMolar). At shear stresses above o.6 Pa, the RISA is identical to controls, but is oxmsiderably less pronounced at lower shear stresses (T < 0.2 Pa). Thus, drugs of completely olifferent pharmacological action produce clear cut rheological effects on RBC in the micrcmolar concentration range; the combination of methods employed opens new possibilities for the systematic development of haemorheologically active drugs.Supported by DFG:Grant Gr 902/1-1