To study the relationship between childhood obesity, weight loss, hyperinsulinaemia and the erythrocyte insulin receptor, we measured the plasma concentrations of immunoreactive insulin (IRI) and C-peptide and the binding of 12sIinsulin to erythrocytes in 12 obese children with a mean age _+ SD of 11.4 + 2.5 years and a mean relative weight score + SD of 4.8 + 1.4 and 12 age-matched normal-weight children. Eight obese children were re-evaluated after i year's participation in a weight reduction programme. The obese children had higher fasting plasma concentrations of IRI (P< 0.01) and C-peptide (P< 0.05) and a lower C-peptide to IRI molar ratio (P < 0.01) than the normal-weight children. The obese children had in addition a reduced erythrocyte insulin binding (P < 0.05 or less) over the physiological range of circulating insulin concentration. There was a negative correlation (r = -0.60; P < 0.01) between the insulin tracer binding and the relative weight. The weight reduction programme resulted in a decrease of 1.0 SD (P < 0.05) in the mean relative weight score. At the end of the therapy the obese children had lower fasting blood glucose levels (P<0.05) and lower plasma IRI concentrations at 90 min (P < 0.05) after an oral glucose load than at the onset of therapy. There were no significant differences between the insulin binding characteristics at the commencement and at the end of the treatment. The low C-peptide to IRI molar ratio in obese children provides evidence of a decreased insulin clearance likely to contribute to their hyperinsulinaemia. The inverse relationship between insulin tracer binding and relative weight suggests a mechanism by which weight changes may be directly reflected in the peripheral insulin sensitivity. A moderate weight loss reduces hyperinsulinaemia in childhood obesity but does not normalize the impaired binding of insulin to its receptor.