Monocyte insulin receptor binding has been shown to be inversely correlated with basal insulin concentrations in a variety of clinical conditions and is believed to reflect autoregulation of receptor properties of insulin. We examined the insulin receptor in the infant of the gestational diabetic mother (IGDM) where hyperinsulinism has been implicated in the attendant metabolical abnormalities. Insulin concentrations in plasma of cord blood of IGDM were significantly greater than in normals delivered between 36-38 weeks by elective cesarean section (101.3 +/- 9.8 vs. 59.9 +/- 9.4 microU/ml; P less than 0.005). [125I]Insulin binding to receptors of monocytes obtained from cord blood showed that IGDM had more receptor sites per monocyte than normal adults and normal infants. In normal infants of similar gestational age, a significant correlation was found between birthweight and binding which was not observed in IGDM. Monocytes from both normal infants and IGDM showed greater affinity for insulin than those from adults. At plasma insulin concentrations of 1 and 4 ng/ml, monocytes from IGDM had about 10 times and normal infants had about 4 times as many sites occupied as those from normal adults. Monocytes from IGDM seem to develop increased concentrations of insulin receptors with hyperinsulinemia. Thus, despite increased ambient levels of insulin, monocytes of IGDM seem to develop increased concentrations of insulin receptor as well as increased affinity for the hormone.