OBJECTIVE: To evaluate the influence of family history of hypertension on insulin sensitivity in obese normotensive adults, comparing them with lean subjects. SUBJECTS: 136 normotensives (N)(mean 24 h blood pressure < 130/80 mmHg; age range 35 - 45 y): 32 lean (body mass index, BMI less than or equal to 25 kg/m(2)) N with normotensive parents (F-), 37 lean N with one or two parents hypertensive (F+), 32 obese (BMI greater than or equal to 30 kg/m(2)) NF- and, 35 obese NF+. METHODS: 24 h ambulatory blood pressure monitoring; glucose, insulin and C-peptide before and 30, 60, 90 and 120 min after an oral glucose load; index of insulin peripheral activity (la: 10(4)/insulin x glucose values at glucose peak); fasting insulin/C-peptide ratio (I/Cp). RESULTS: The four groups were comparable for age, gender and blood pressure values throughout the 24 h. Glucose, fasting and during test, and I/Cp were similar among the four groups; insulin and C-peptide, fasting and stimulated, were significantly higher and la lower in obese N than in lean N; at similar BMI, insulin and C-peptide were significantly higher and la lower, in F+ than in F-. The correlation between insulin and BMI was significantly closer in F- than in F+. CONCLUSIONS: Family history of hypertension appears to be significantly associated with insulin sensitivity in both lean and obese normotensive adults; moreover, overweight and a genetic predisposition to hypertension may have additive adverse effects on insulin sensitivity in normotensive adult subjects.