To determine the association between the -265 T to C substitution in the apolipoprotein A-II (APOA-II) gene and levels of visceral adipose tissue (VAT) in a group of premenopausal African-American and white women, we genotyped 237 women (115 African-American and 122 white) for this polymorphism. Body composition was assessed by DXA, and VAT was determined from a single computed tomography scan. In addition to VAT, we examined the association between the polymorphism and other phenotypes (total body fat, total abdominal adipose tissue, and subcutaneous abdominal adipose tissue). The mutant C allele in the APOA-II gene was less frequent in African-American compared with white women, 23% vs. 36%, respectively (p < 0.01). VAT was significantly higher in carriers of the C allele compared with noncarriers after adjustment for total body fat (p < 0.05). When separate analyses by ethnic group were conducted, the association between the polymorphism and VAT was observed in white (p < 0.05) but not African-American (p = 0.57) women. There was no association between the polymorphism and the other phenotypes. These results indicate a significant association between the T265C APOA-II polymorphism and levels of VAT in premenopausal women. This association is present in white but not African-American women.