The objective of this study was to examine the influence of positive family history (FH) of type 2 diabetes (T2D) on aspects of insulin resistance in prepubertal children. Twenty-one children (Tanner stage I or II) with a positive FH were compared with children with no FH. FH was defined by presence of T2D in a parent or grandparent as assessed by interview. The two groups of children were matched for age, gender, Tanner stage, ethnicity, geographical location, and body fat mass using a pair-matched design. These 21 pairs of children included Caucasian, African American, and Hispanic children who were studied either in Birmingham, Alabama, or Los Angeles, California, using similar techniques. Insulin sensitivity (S(I)) and the acute insulin response to glucose (AIR) were determined by an iv glucose tolerance test and minimal modeling, and body composition was determined by dual-energy x-ray absorptiometry. There were no significant differences in fasting glucose or insulin, S(I), AIR, the disposition index (product of S(I) and AIR), or body composition between children with a FH vs. those without a FH of T2D, and there were no significant differences in these parameters when the data were analyzed separately in each ethnic group. In conclusion, a positive FH for T2D does not seem to have any significant effect on insulin sensitivity, as assessed by the minimal model and associated risk factors for T2D in young children.