The effects on membrane lipid composition of chronicin vivoexposure of adult cells to a fetal plasma environment were studied in eight infants who received repeated intrauterine transfusions for erythroblastosis fctalis. Comparison is made between the lipid composition of the transfused adult cells obtained at delivery and the lipid composition of cells from normal newborn infants, from nontransfused newborn infants with erythroblastosis (EB), and from adult donor cells. Transfused cells which had circulated in the fetus for a minimum of 5–16 days showed a significant increase in membrane cholesterol (transfused cell cholesterol 1.53 mg/cell X 10-10; donor cell cholesterol: 1.26 mg/cell X 10-10). One patient in whom donor cells circulated a minimum of 30 days showed increased levels of total lipid (6.73 mg/cell X 10-10) and lipid phosphorus (1.35) mg/cell X 10-11) as well as cholesterol (1.74 mg/cell X 10-10). These increases in membrane lipid content were not accompanied by increased cell volume.Phospholipid distribution in cells circulating the shorter period was similar to that seen in donor cells except for a lower percentage of combined phosphatidyl serine + phosphatidyl inositol (transfused cells: 10.6% total phosphorus, donor cells: 13.5% total phosphorus). The patient with longer cell circulation had an abnormal phospholipid distribution, similar to that seen in hepatic disease (phosphatidyl choline: 44.4% total phosphorus; donor phosphatidyl choline: 28.4% total phosphorus), and subsequently developed elevated levels of direct bilirubin.Phospholipid fatty acid distribution in the transfused cells more closely resembled the fetal pattern with low levels of linoleic acid (transfused: 5.7% of total fatty acids; donors: 10.0% of total fatty acids). Sensitivity of the transfused erythrocytes to hydrogen peroxide hemolysis was elevated in three patients (fetal cell pattern) and low in three patients (adult cell pattern). Lipid values in plasma were similar in transfused patients, in nontransfused infants with EB, and in normal infants except for slight elevations of total phospholipid in the transfused group.SpeculationThe concept that fetal erythrocytes containing fetal hemoglobin are necessary for intrauterine life would appear untenable inasmuch as it is now apparent that adult erythrocytes with adult hemoglobin can maintain fetal viabilityin utero. Because many of the functional characteristics of the fetal crythrocyte are more directly related to the presence of a fetal red cell membrane than to the presence of fetal hemoglobin, it is possible that the efficacy of adult cellsin uteromay, in part, be related to an ability to adapt to a fetal environment. These studies demonstrate a tendency for transfused adult erythrocytes to alter certain aspects of their lipid composition when exposed to a fetal plasma environmentin vivo