The Gly972Arg substitution of the insulin receptor substrate-1 (IRS-1) gene and the Pro12Pro genotype of the peroxisome proliferator-activated receptor gamma 2 (PPARgamma2) gene have been suggested to be associated with type 2 diabetes mellitus. In this study, the influence of these two polymorphisms on serum adiponectin concentrations was investigated. The Pro12Ala polymorphism of the PPARgamma2 gene and the Gly972Arg polymorphism of the IRS-1 gene were genotyped in 252 young Finnish servicemen. The Ala12Ala genotype of PPARgamma2 was associated with a higher adiponectin level compared to the Pro12Ala genotype (p=0.02) and the Pro12Pro genotype (p=0.02). Total (p=0.02) and low-density lipoprotein (LDL) cholesterol (p=0.03) levels were higher in subjects with the Pro12Pro genotype compared to the Pro12Ala genotype. No difference was observed in serum adiponectin level between the IRS-1 genotype groups. The subjects with X972Arg of this gene had high total and LDL cholesterol levels (p<0.05). The interaction between the PPARgamma2 and IRS-1 genes with respect to their effects on adiponectin levels was statistically significant (p=0.02). Adiponectin was significantly higher (p<0.05) in subjects who simultaneously had the Ala/Ala (PPARgamma2)+Gly/Gly (IRS-1) genotype combination compared to subjects with the Pro/Pro+Gly/Gly and Pro/Ala+Gly/Gly genotype combinations. Total and LDL cholesterol was higher (p<0.05) in subjects with Pro/Pro+X/Arg compared to subjects with the two before mentioned genotype combinations. We conclude that the Ala12Ala genotype of PPARgamma2 is associated with elevated adiponectin level, and that the PPARgamma2 and IRS-1 genes have a possible interaction in their effects on adiponectin concentration.