To investigate the possibility of altered digoxin receptor binding properties in neonates, we compared digoxin binding with erythrocytes from neonates and adults. Neonatal erythrocytes had two and a half times as many digoxin binding sites as adult erythrocytes. The neonatal "receptors" also had dissociation constants for digoxin that were twice the adult value. These findings suggest that differences in binding properties may explain the clinical observation of decreased sensitivity to digoxin in neonates and infants.