Insulin resistance, the most important factor in metabolic syndrome X, has been considered to raise blood pressure. Recently it was reported that insulin resistance was related to an elevated plasma level of leptin, which is an adipocyte-specific ob gene product and which plays a role in food intake suppression, thermogenesis, and energy expenditure through the activation of the hypothalamus. However there are no reports that deal with the relationship of insulin resistance to plasma leptin and blood pressure. To evaluate the role of leptin in essential hypertensives, two groups of subjects who were carefully matched for body mass index (BMI) were studied; 22 normotensives (NT, age: 46.5 +/- 2.6 years, BMI: 23.9 +/- 0.4 kg/m2, male/female: 14/8) and 45 mild-to-moderate essential hypertensives (EHT, age: 51.9 +/- 2.0 years, BMI: 24.5 +/- 0.4 kg/m2, male/female: 21/24). We applied the euglycemic hyperinsulinemic glucose clamp technique to all subjects and insulin sensitivity was evaluated as the M value. EHT showed a significantly lower M value (160.2 +/- 7.4 v 184.3 +/- 7.3 mg/m2/min, P < .05) and higher basal plasma immunoreactive leptin level (7.6 +/- 0.8 v 5.0 +/- 0.8 ng/mL, P < .05) than NT, despite the fact that there was no significant difference between NT and EHT in age, gender, or BMI. The relationship between mean blood pressure and leptin showed a significant positive correlation in all of the subjects (r = 0.31, P < .05), suggesting that leptin may be related to a pathophysiology of essential hypertension.