OBJECTIVE: Obesity is associated with a high risk of hypertension and is characterized by hyperaldosteronism and hypercortisolism. We have previously reported that patients with resistant hypertension (RHTN), defined as blood pressure (BP) that remains above goal in spite of the concurrent use of 3 antihypertensive agents of different classes, have a high prevalence of hyperaldosteronism that is positively correlated with body mass index (BMI). Experimental studies indicate that adipocytes secrete a as yet undetermined factor that stimulates aldosterone and cortisol release. Our objective was to determine in patients with RHTN if obesity as indexed by BMI is positively correlated with both 24-hour urinary aldosterone (24 h U-Aldo) and cortisol (24 h UCort) levels. DESIGN AND METHOD: Cross-sectional study of a cohort of 745 patients with RHTN referred to the Hypertension Clinic at the University of Alabama at Birmingham. All patients underwent 24 h U-Aldo and 24 h UCort evaluation. RESULTS: Characteristics of the cohort were 50% females, 40% African Americans, BMI = 32.7 ± 6.9 kg/m, systolic BP = 157.8 ± 25.6 mmHg, and diastolic BP = 87.6 ± 14.9 mmHg, and average number of medications 4.2 ± 1.2. 24 h UAldo (p = 0.0007) and 24-h UCort levels (p = 0.01) were both positively correlated across tertiles of BMI for the entire cohort. When analyzed by gender there was no difference in BMI but men had significantly higher UCort levels (161 ± 93 versus 120 ± 66 μg, p < 0.001) and the relation was stronger in men than women (r = 0.12 vs 0.08, p < 0.05) suggesting that visceral adipose tissue more characteristic of men is an important mediator. When analyzed by race there was no difference between Caucasian and African American subjects. CONCLUSIONS: Aldosterone and cortisol levels were positively related to BMI and higher in men than women suggesting that obesity, particularly visceral adiposity, contributes importantly to increases in both hormones possibly secondary to a common adipocyte-derived stimulus.