The binding characteristics of insulin-like growth factor I on erythrocytes were studied in 11 patients with long-term IGF-I deprivation and low serum IGF-I levels. Six patients had Laron type dwarfism and 5 idiopathic isolated growth hormone deficiency, with a mean (±SEM) serum IGF-I level of 6.01±1.01 nmol/l. as compared with that in 25 normal controls of 26.35±2.73 nmol/l (p=0.00001). The mean (±SEM) [125I]IGF-I specific binding at a concentration of 4x1012 cell/l was 12.11±1.29% for the patient group compared with 8.75±0.62% for the controls (p=0.005). Scatchard analysis showed a curvilinear plot. Using a non-linear curve fit, the mean (±SEM) number of high-affinity receptor sites per cell was found to be 7.34±1.80 in the IGF-I deprived patients and 2.84±0.29 in the controls (p=0.0005). The mean ±SEM dissociation constant was found to be 0.33±0.10 nmol/l for the patients and 0.26±0.08 nmol/l for the controls (NS). This study has demonstrated that the low serum concentration of IGF-I in Laron type dwarfism and isolated growth hormone deficiency is associated with an increase in receptor sites for IGF-I on the erythrocytes. The application of this property as a diagnostic aid remains to be established.