OBJECTIVE—We studied the association between the Gly972Arg polymorphism in insulin receptor substrate-1 (IRS-1) and birth weight in a population-based sample of Brazilian newborns. RESEARCH DESIGN AND METHODS—We studied 194 newborn children with adequate gestational age to identify the association between the Gly972Arg polymorphism and birth weight using PCR—restriction fragment length polymorphism analysis. RESULTS—The data showed that the birth weight was lower in the newborns with the Gly972Arg polymorphism in IRS-1 compared with control subjects (3,141 ±31.8 vs. 3,373 ±80.3 g, P < 0.008). The results also showed that the frequency of this polymorphism was increased in newborns with a birth weight <3,000 g (P=0.041). CONCLUSIONS—These results suggest that the genotype Gly972Arg may influence birth weight, reinforcing the hypothesis that genetically determined insulin resistance and/or reduced insulin secretion can result in impaired insulin-mediated growth in the fetus.