The insulin resistance syndrome has been characterized by hypertension, upper body obesity, insulin resistance, hyperinsulinemia, glucose intolerance, and hypertriglyceridemia. Previous studies are inconsistent regarding the relationship between blood pressure and insulin resistance. We therefore compared the metabolic profile in 60 hypertensive subjects (mean+/-SD arterial pressure, 116+/-7 mm Hg) and 60 normotensive subjects (mean arterial pressure, 88+/-5 mm Hg) matched for age, gender, and body mass index. Hypertensives had significantly higher waist-to-hip ratio than normotensives (P=0.002). The groups did not differ in fasting plasma glucose (0.2 mmol/L, P=0.09), insulin (6 pmol/L, P=0.14), insulin sensitivity index (-0.01 micromol x kg(-1) x min(-1) x pmol/L(-1), P=0.7), and suppression of nonesterified fatty acids during a hyperglycemic clamp (1%, P=0.40). There were significant differences in fasting levels of C-peptide (50 pmol/L, P=0.004) and proinsulin (2 pmol/L, P=0.01), 2-hour postload levels of glucose (0.8 mmol/L, P=0.01) and insulin (84 pmol/L, P=0.01) after oral glucose challenge, and hepatic glucose production during the clamp (2.87 micromol x kg(-1) x min(-1), P=0.02). These differences were not significant when controlling for waist-to-hip ratio. Body mass index and waist-to-hip ratio were similarly associated with the insulin sensitivity index in the hypertensive (r=-0.59, P=0.0001 and r=-0.32, P=0.05) and normotensive (r=-0.58, P=0.0001 and r=-0.39, P=0.05) groups. Hypertension per se is not associated with insulin resistance. However, even small increments in both body mass index and waist-to-hip ratio, as often seen in hypertension, may lead to impairment in insulin sensitivity, probably mediated through altered lipid metabolism.