The insulin (INS) and IGF 2 (IGF2) genes are in close proximity to each other and undergo maternal imprinting during fetal growth. We investigated the association between maternal and umbilical cord IGF 2 protein (IGF-II) levels and single nucleotide polymorphisms (SNPs) in the INS and IGF2 genes in 207 healthy African-American mother-newborn pairs. No association was found between maternal IGF-II levels and polymorphism in the INS-IGF2 locus. A significant association was found between newborn IGF-II levels and two SNPs (rs3842738 and rs689) at the 5' end of the INS-IGF2 focus. Analyses of haplotypes inferred from these two SNPs demonstrate a significant relationship between paternally transmitted haplotypes and newborn IGF-II levels, but no association with maternally transmitted haplotypes.