It has been proposed that both hypercortisolism and low sympathetic nervous system (SNS) activity contribute to obesity. Because glucocorticoids inhibit SNS activity, we hypothesized that hypercortisolism and low SNS activity may be found in association in Pima Indians, a population with a high prevalence of obesity. We therefore measured indices of hypothalamic-pituitary-adrenal (HPA) axis and SNS activities in 39 nondiabetic men, 20 Pimas (age, 30+/-5 years; weight, 94+/-26 kg; 35%+/-8% body fat [mean +/- SD]) and 19 Caucasians (33+/-9 years, 91+/-23 kg, 28%+/-11% body fat). HPA axis activity was assessed by measurements of morning fasting plasma corticotropin (ACTH) and cortisol concentrations and 24-hour urinary free cortisol (UFC) excretion. SNS activity was assessed as muscle sympathetic nerve activity (MSNA) by microneurography and by measurement of catecholamines (fasting plasma concentration and 24-hour urinary excretion). Plasma ACTH and cortisol and UFC were similar in Pimas and Caucasians. MSNA was positively correlated with percent body fat (r = .49, P = .002) and was lower in Pimas compared with Caucasians after adjustment for percent body fat (24+/-9 v 31+/-10 bursts/min, P = .04). We conclude that Pima Indians, a population with a high prevalence of obesity, have lower SNS activity but normal HPA axis activity compared with Caucasians.