The relevance of the insulin gene (INS) variable number tandem repeat (VNTR) polymorphism to indexes of body size and adult obesity is inconclusive. Given the equivocal reports on the association between the VNTR class genotype at the insulin gene locus and indexes of body size and obesity, we assessed these associations in a series of cohort studies based on 7,999 middle-aged men and women. We found no convincing evidence that INS VNTR class genotype was associated with indexes of body size and adult obesity. These data suggest that INS VNTR class is not an important determinant of size and body weight regulation in middle-aged men and women.