Obesity has a genetic component and predisposes for the development of type 2 diabetes mellitus. One approach to identifying new candidate genes for obesity is to explore potential regulatory factors expressed in fat tissue that may play a role in adipocyte development or metabolic control. Because we found relatively abundant mRNA levels of the putative transcription factor MTG8 in human adipose tissue, a polymorphic microsatellite marker in the 3' untranslated region of this gene was genotyped in 281 Pima Indians, a population with one of the highest reported rates of obesity. We detected a male-specific association with age-adjusted percentage body fat (p = 0.0002), body mass index (p = 0.01), waist circumference (p = 0.008), and thigh circumference (p = 0.02). Comparative analysis of all 13 MTG8 exons in 30 Pimas did not reveal any genetic variants which could explain the association with obesity in males.