Red blood cell (RBC) deformability in rats of various ages was assessed by filtration (3 μm Nuclepore membranes). Neonatal rat RBC (1 d old) had lower filter-ability, both in terms of RBC incremental volume (9.97 ± 1.85 versus 0.33 ± 0.28 nL at 180 d of age, mean ± SD, p < 0.001) and the number of filter clogging particles (25.7 ± 3.1 versus 18.9 ± 3.4 RBC × 103/s, p < 0.001). The lower filterability correlated with a larger RBC volume (169 ± 12.6versus69 ± 3.2 μm3, pversus2.84 ± 0.05 μm, p < 0.001). Almost all of the neonatal RBC had a minimum cylindrical diameter exceeding the 3 μm nominal pore size of the filters. The calculated resistance to initial folding was also significantly greater, as indicated by a static bending analysis of initial deformation. However, when the larger size of neonatal RBC was taken into consideration, and thus their greater projected area on which forces are applied, they appear to be at least as deformable as the adult type RBC. This finding may explain the contradiction between RBC filtration experiments and other approaches based on RBC deformations in shear flow, which have been unable to detect a hampered flexibility of neonatal RBC. In view of the more pronounced differences between neonatal and adult RBC in rats than in human subjects, the rat is an interesting model for studying this physiologic phenomenon in newborns.