A common polymorphism (C825T) of the gene encoding the G-protein beta(3) subunit has been associated with obesity. We examined the hypothesis that this polymorphism affected weight gain during pregnancy. Two hundred and ninety-four women with uncomplicated term deliveries of singleton pregnancies were genotyped. Women homozygous for the T allele (TT) gained significantly more weight than women carrying the C allele (CC and CT groups) (P = 0.006) and had a significantly higher pre-pregnancy body mass index (P = 0.02). The C825T polymorphism of the G-protein beta(3) subunit gene, known to be associated with obesity, is a determinant of weight gain during pregnancy.