Cord sera were obtained from term, Chilean newborns exhibiting various patterns of intrauterine growth and assayed for IGF-1, IGF-2, IGFBP-1, IGFBP-2, and IGFBP-3 by specific radioimmunoassays (RIA). Serum levels of each peptide were correlated with birth weight (BW), ponderal index (PI), and placental weight (PW). Total IGF-1 levels correlated with BW (r = 0.665, P = 0.0001). PI (r = 0.527, P = 0.004), and PW (r = 0.596, P = 0.0017). In contrast, IGF-2 failed to correlate with any growth parameter. Of the three binding proteins, IGFBP-3 exhibited the strongest relationship to each growth parameter. IGFBP-3 correlated significantly with BW (r = 0.71, P < 0.0001), PI (r = 0.782, P < 0.0001), and PW (r = 0.57, P = 0.0029). In addition IGFBP-3 levels positively correlated to IGF-1 levels (r = 0.614, P = 0.0005). By contrast, circulating IGFBP-1 and IGFBP-2 were inversely related to IGF-1 levels. All five peptides were subjected to multiple regression analysis and related to BW. Significant relationships between the predicted BW and the actual BW were observed in these infants (r = 0.802, P = 0.0006). The BWs of a cohort of unrelated North American infants were also predicted using the Chilean-derived equation and found to be significantly related to their actual BWs (r = 0.453, P = 0.0033). These relationships were strengthened by the inclusion of estimated gestational age (EGA) as an independent variable. These data point to particularly important roles for IGF-1 and IGFBP-3 in regulating fetal growth at term, and suggest that they are regulated in a coordinated manner during the latter stage of gestation. Furthermore, they suggest that IGFBPs play multiple, and potentially opposing, regulatory roles in modulating IGF action. Lastly, an integrated expression of IGF activity derived from one population significantly correlated with newborn BW in a geographically and culturally distinct population.