The deformability of neonatal and adult red blood cells (RBC) was studied using both unseparated and density (i.e., age) fractionated RBC. Blood samples were obtained from 10 normal newborn infants (placental blood) and 10 adults. Deformability was measured by direct microscopic observation of RBC subjected to shear stresses of 2.5-500 dynes/cm2 using a counter-rotating Rheoscope. There was no significant difference in deformability between unseparated neonatal and adult RBC at any shear stress. The 3% least dense ("youngest") RBC showed significantly decreased hemoglobin concentrations (MCHC), increased volumes (MCV) and elevated deformability at any shear stress when compared to the 3% most dense ("oldest") cells, with the values for the unseparated RBC lying between these two extremes. The least dense neonatal RBC had a significantly lower MCHC and higher deformability than the least dense adult cells; however, the most dense neonatal RBC had lost more volume than the adult cells (33 versus 17%), had a higher MCHC, and were less deformable than the most dense adult cells. This indicates that the accelerated decrease in deformability of aging neonatal RBC is related to the more pronounced increase in MCHC, which is the principal determinant of the internal viscosity of the RBC.