Insulin binding to erythrocytes from normal subjects over a wide range of ages (group I, cord blood; group II, Age 6M to 6 yrs; group III, 7 to 19 yrs; group IV, 20 to 59 yrs, group V, over 60 yrs of age) was determined using modified Gambhir's method and the effect of age and sex on the binding was evaluated. The highest insulin binding to cord blood erythrocytes was accounted for by the increased number of reticulocytes since there was a highly significant correlation between insulin binding and the reticulocyte count (r = 0.928, p less than 0.001). Group IV showed significantly higher binding than younger are groups II and III. The mean binding in group V was the highest among all age groups except for group I, although the differences failed to reach statistical significance. The receptor concentrations (R0) were comparable among groups except group I which had a slightly increased R0. The affinity of insulin receptors was the lowest in group I and II, and gradually increased with the age and a positive correlation (p less than 0.01) was obtained between age and Ke. This increase in affinity with age is considered an adaptive response to the intracellular metabolic derangement often seen in the aged. No effect of sex on insulin binding was seen before puberty. However, in normal adults insulin binding of the female tended to be lower than that of the male with slightly increased R0 and decreased affinity in the female. Thus, the slightly decreased binding of the female group was mainly accounted for by the decreased affinity although the difference in the affinity was not significant.