Previously reported data obtained by electron spin resonance (ESR) assays demonstrated a lower availability of membrane sulfhydryl reacting groups in the erythrocytes of cord blood than in those of blood drawn after 4 days of life (Bracci et al. Pediatr Res 1988; 24:391). This finding was observed in red cells suspended in plasma. In the attempt to ascertain if the peculiarity of cord blood erythrocytes is due to a stable modification of the membrane structure or transitory interactions between membrane and plasma components, MAL-6 ESR assays were carried out in erythrocyte ghosts of cord blood and blood of 4 day old infants. The analysis of ESR spectra clearly demonstrate particular pattern at birth suggestive of significantly increased aggregation of spectrin in the cord blood red cells. After 4 days of life no significant differences between adult and infant spectra were observed. These important variations in the state of the erythrocyte membrane skeletal protein network may play a role on the changes of the rheological properties of newborn blood which have been reported to occur during the first days of life.