Adiponectin, coded for by the APM1 gene, is a novel adipocyte-derived hormone implicated in energy homeostasis and obesity. Several genetic studies have observed evidence of association between APM1 gene polymorphisms and features of the metabolic syndrome, such as insulin resistance and obesity. As part of a comprehensive genetic analysis of the APM1 gene, we have screened 96 unrelated individuals for polymorphisms in the promoter, coding regions, and 3untranslated region (UTR). Three promoter single-nucleotide polymorphisms (SNPs), two rare coding SNPs (G113A and T1233C), and 13 SNPs in the 3UTR were identified. Eighteen SNPs were genotyped in 811 Hispanic individuals from 45 families in the IRAS Family Study (IRASFS). SNPs were tested for association with six obesity quantitative traits (body mass index, waist, waist:hip ratio, subcutaneous adipose tissue, visceral adipose tissue, and visceral:subcutaneous ratio). Significant evidence of association to at least one of the obesity traits was identified in seven of the 18 SNPs (<0.001–0.05). the="" promoter="" snp="" ins="" ca-11156="" was="" the="" most="" consistently="" associated="" snp="" and="" was="" associated="" significantly="" with="" all="" measures="" of="" obesity,="" except="" the="" visceral:subcutaneous="" ratio="">P-values 0.009–0.03). Haplotype analysis supported this evidence of association, with haplotypes containing an insertion of one CA repeat at position –11156 consistently being associated with lower obesity values (P-value <0.001–0.05). the="" adiponectin="" polymorphisms,="" in="" particular="" those="" in="" the="" promoter="" region,="" thus="" show="" significant="" association="" with="" obesity="" measures="" in="" the="" hispanic="" population.="" additional="" studies="" are="" needed="" to="" confirm="" our="" findings="" and="" determine="" which="" polymorphism="" causes="" the="" functional="">