The erythrocyte destruction rate under constant shear stress was measured to clarify species differences in red blood cell (RBC) mechanical fragility between human, bovine, and ovine cells. Blood was collected from healthy donors by venipuncture. RBC age fractionation was performed by high speed centrifugation (20 min at 12,000 g). Relatively young, middle, and old age RBCs was suspended in Dulbecco's phosphate buffered saline to adjust the hematocrit to 35%. Uniform shear stress was applied to each sample contained in a concavo-convex Couette flow testing machine. Young and old aged samples were exposed to 300 dyne-sec-cm2 for 0 and 15 min. Middle aged samples were exposed to 300 dyne-sec-cm2 for 0, 5, 10 and 15 min. Liberated hemoglobin was estimated by tetramethylbenzidine colorimetric measurement and the erythrocyte destruction rate was calculated. Older samples had a higher hemolysis rate than younger samples in every species. The destruction under constant shear stress is approximately linear in time. Mechanical fragility of ovine and bovine RBCs was 1.8 and 0.5 times as large as human RBCs, respectively. These values could serve as universal standards when extrapolating animal hemolysis data for any blood pump to predict its safety and biocompatibility in human clinical trials.