Young children are growing at a time when circulating levels of IGF-I measured by RIA are generally less than or equal to values in nongrowing adults. 125I-Thr59-IGF-I binding to receptors on conveniently available red blood cells was studied in 33 normal adults (nine males, 24 females) and 13 normal prepubertal children aged 3-10 y (10 boys, three girls; all Tanner stage 1). Red blood cell specific binding of 125I-Thr59-IGF-I was determined by displacement of labeled Thr59-IGF-I by unlabeled Thr59-IGF-I or insulin in a dose-dependent manner. Mean (+/- SEM) 125I-Thr59-IGF-I specific binding was significantly higher (p = 0.01) in prepubertal children than in adults (13.9 +/- 0.7% versus 11.6 +/- 0.5%/3 x 10(9) cells/mL). Specific binding did not differ between adult males and females. There was no significant correlation between specific binding and reticulocyte count. Scatchard analysis demonstrated a linear plot. Increased binding to red blood cells in the prepubertal children appeared to be due to an increase in receptor affinity (Ka = 4.97 +/- 0.42 x 10(8) M-1 versus 3.70 +/- 0.41 x 10(8) M-1; children versus adults; p = 0.03). Mean receptor concentrations were not different in children and adults (64.4 +/- 8.5 versus 58.0 +/- 5.6 binding sites/cell). There was a significant positive correlation between 125I-Thr59-IGF-I specific binding and affinity (p = 0.007, r = 0.39). We speculate that the greater specific binding of labeled Thr59-IGF-I to red blood cells in prepubertal children may provide a mechanism for enhanced cellular responsiveness to relatively low levels of circulating IGF-I.