OBJECTIVE: To examine whether the association between abdominal obesity and hyperglycemia differs according to the presence of a parental history of diabetes. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional study of 3,068 men and women, aged 20-65 years, without known diabetes who were fasting participants of a population-based study in three Dutch towns. Hyperglycemia was defined as a fasting plasma glucose concentration of 6.1 mmol/l (American Diabetes Association criterion). Waist circumference was categorized according to previously defined waist action levels. All estimates were adjusted for age and town. RESULTS: The regression coefficients for the association between waist circumference and fasting plasma glucose were larger in participants who had a parental history of diabetes than in those who did not (men beta = 0.31 vs. 0.16 mmol/SD, P [for interaction] = 0.003; women beta = 0.24 vs. 0.11 mmol/SD, P = 0.002). Furthermore, larger waist circumference (men > or = 94 vs. < 94 cm, women > or = 88 vs. < 80 cm) was associated with a greater excess prevalence of hyperglycemia in participants who had a parental history of diabetes than in those who did not (men 12.4 vs. 2.0%, P = 0.03; women 13.6 vs. 5.9%, P = 0.05). Adjustment for physical activity, alcohol intake, smoking, and educational level did not materially change the results. CONCLUSIONS: These findings indicate that the association between abdominal obesity and hyperglycemia is stronger in the presence of a parental history of diabetes. Blood glucose screening may be warranted at lower levels of waist circumference in individuals with a parental history of diabetes.