The effects of pentoxifylline and other hemorheologically active drugs on the human erythrocyte membrane were examined by means of electron spin resonance spectroscopy. It was observed that the fluidity in the region of the phospholipid head groups in the erythrocyte bilayer was increased by an externally added drug. In this region, membrane fluidity was dependent on the incubation time, suggesting an interaction with membrane proteins. On the other hand, the acyl chain motion in the lower portion of the chain, the hydrophobic end, was reduced in the presence of the drugs. In this case, the acyl chain motion was not time-dependent. These changes of the membrane fluidity at different depths of the membrane induced by the drugs may correlate to the erythrocyte deformability.