Erythrocytes (RBCs) from cord blood are known to bind more insulin than those of adults. We have investigated the possibility that this difference is due to the younger cell age of the neonatal cells. Samples from 13 normal full term neonates and 12 adults were fractionated into 5 fractions of defined density by dextran gradient centrifugation. Fractions of comparable density, a variable known to correlate well with age, were then compared for insulin binding. Plasma insulin and glucose levels were the same in the two study groups. The density distribution curve was shifted to the left for the cord samples, indicating a younger cell age. The difference was most marked in the lightest fraction, which contained 4.66 + 0.46% (mean +/- SE) adult cells vs. 15.26 +/- 1.27% cord cells (P less than 0.01). Insulin binding was identical when fractions of equal density were compared in the two groups. The only exception was the lightest (youngest) fraction (density, less than 1.092), in which the cord cells displayed a considerably higher percentage of specific binding; (19.98 +/- 1.57 vs. 13.32 +/- 0.92 P less than 0.005). This difference was shown to be due to a high percentage of very light cells in cord samples, compared to adult samples, in this fraction which, unlike the others, did not have a lower limit of density. When a lower density cutoff was introduced (1.089 g/ml), the remaining cells of this fraction (density, 1.089-1.092) displayed quite similar percentages of specific binding (13.07 +/- 1.63 vs. 11.86 +/- 1.27). Cells below this density were virtually absent in the adult, comprising less than 0.3% of all adult cells compared to 7.2% of the cord cells. These results indicate that the difference in insulin binding between adult and cord cells is due to a younger RBC age distribution in cord blood. This difference is most marked in the youngest cell fractions. Age fractionation of RBCs by density gradient centrifugation appears to be a promising method of assessing RBC insulin receptors in situations in which substantial changes in cell age are seen.