Body size at birth is an indicator of the intrauterine environment. The effects of the Pro12Pro genotype and the 12Ala allele of the PPARγ-2 gene on glucose and insulin metabolism in adult life depend on body size at birth. A low birth weight is associated with insulin resistance and type 2 diabetes. The peroxisome proliferator-activated receptor-γ (PPARγs) are also regulators of adipocyte differentiation, and the PPARγ-2 gene could also contribute to the development of dyslipidemia. Therefore, the effects of the Pro12Ala polymorphisms of the PPARγ-2 gene on lipid metabolism were measured in 476 elderly persons whose birth weight was known. The Ala12 allele was associated with increased serum total, low-density lipoprotein (LDL), and non-high-density lipoprotein (non-HDL) cholesterol concentrations but only among those who had birth weights below 3000 g. These interactions between the effects of the PPARγ-2 gene on adult traits and the effects of birth weight may be interpreted as examples of gene–environmental interactions, which underlie plasticity during development.