Infants of diabetic mothers are frequently iron deficient at birth on the basis of increased fetal iron demand and reduced placental iron transport. We previously showed reduced binding affinity for transferrin (Tf) by transferrin receptor (TfR) isolated from diabetic placentae. The effect was directly related to the degree of fetal glycemia. Since proper glycosylation is important for normal Tf binding by TfR, we tested the hypotheses that 1) placental TfR molecular weight (MW) is higher in diabetic pregnancies, 2) increased TfR MW is related to increased glycosylation related to fetal hyperglycemia, and 3) impaired 125I-Tf binding is related to increased TfR MW. TfR was isolated from membranes of 9 term diabetic and 5 non-diabetic human placentae. Competitive TfR binding to 125I-Tf was assessed by Scatchard analysis. TfR was isolated on a CNBr Sepharose 4B anti-transferrin column; MW was determined by SDS-PAGE. TfR was identified on Western blot using a polyclonal antibody (courtesy of Dr. C. Enns, University of Oregon). Two bands were identified in all samples. The mean ±SD MW of the larger TfR was greater in the diabetic group compared to control (91.7±1.5 vs 87.1±3.2 KD; p=0.02) and correlated with the cord [C-peptide] (r=0.55; p=0.03). Although the MW of the lighter TfR was not different between groups(diabetic: 83.7±0.7 vs C: 83.1±0.8), this species also correlated with cord serum [C-peptide] (r=0.52; p=0.05). Cord [C-peptide] was higher in the diabetic group (0.7±0.4 vs 0.3±0.2 μmol/l) and correlated with the TfR Kd (r=0.68; p=0.005). TfR Kd was higher in the diabetic group (7.83±4.3 vs 5.7±1.9 nmol/l); however, no relationship was found between either TfR species MW and Kd. We conclude: 1) TfR isolated from diabetic placentae are heavier, most likely due to increased glycosylation. 2) The reduced binding affinity for Tf appears unrelated to the TfR size, and thus glycosylation status. Supported by NICHD.