The rheological action of aspirin on human erythrocytes was studied by in vitro incubation of normal erythrocytes with aspirin at 1, 2 and 4 mg/ml for 30-60 min and then measuring erythrocyte rheological properties of deformability, osmotic fragility and aggregation. Aspirin (2 and/or 4 mg/ml) significantly (p<0.05) prevented the loss of filterability (deformability) through 5 microm diameter pores of erythrocytes dehydrated with hypertonic buffer (450 mOsm/kg water) or with potassium ionophore valinomycin (18 micromol/l). When the calcium ionophore A23187 (1.9 micromol/l) was used to induce cell dehydration, aspirin (4 mg/ml) unexpectedly significantly (p<0.05) increased further the loss of filterability (deformability). Aspirin (1, 2 and 4 mg/ml) also increased significantly (p<0.05) erythrocyte osmotic fragility. Aspirin (4 mg/ml) had no effects on aggregation of erythrocytes induced by dextran 70 (3%). The results suggest that aspirin could play a rheologically active role on erythrocytes. The observed effects of aspirin could be explained by acetylation of intracellular proteins and hence saturation (concentration) of the cell interior with the osmotically active drug.