Transforming growth factor-alpha (TGFα) is a polypeptide that plays an important role in the growth and differentiation of a variety of ectodermal and mesodermal cells both during fetal and postnatal life. Epidermal growth factor (EGF), a growth factor that acts similarly to TGFα through binding of the EGF receptor, is associated with fetal growth and maturation: EGF cord blood concentrations correlate significantly with birth weight and placental weight (Biol Neonate, 1992:61). It is unknown if a similar relationship exists between cord blood TGFα concentration and advancing gestational age. We sought to determine if such an association exists. Eighty newborns ranging in age from 26 to 42 weeks gestation were enrolled in the study, and clinical data collected prospectively. At delivery, a cord blood sample was collected from each placenta and processed within 4 hours for serum separation. Serum samples were then frozen at -80°C until later analysis. Each sample was analyzed for TGFα concentration (pg/mL) by a commercially available RIA (RDI; sensitivity 1 pg/100 μL; cross-reactivity with EGF of 0%). The concentration of cord serum TGFα was expressed as the mean ± S.D. There was a strong association between TGFα cord serum concentration and gestational age (p<0.0002): the cord serum TGFα mean ± S.D. of infants <35 weeks was 16.5± 6.0 while the mean ± S.D. TGFα concentration of those infants ≥ 35 weeks was 26.0 ± 9.4. TGFα concentration increased with advancing gestational age to 36 weeks; thereafter, a concentration plateau was reached. Post-hoc analysis for unequal cell size was significant at p<0.05 (set a priori) with a critical difference of 3.7 (F=15.4). A similar association was demonstrated with birth weight. Those indicators of a premature birth, such as use of tocolysis, administration of celestone to mother prior to delivery, and respiratory distress, also were associated with TGFα cord serum concentrations. These results suggest that TGFα, like EGF, may play a role in fetal growth, and may be a marker of fetal maturity.