Resting metabolic rate (RMR) comprises 50-80% of daily energy expenditure, and is highly variable between subjects even after adjusting for body weight and body composition. RMR is believed to be genetically determined. Individuals with a low RMR for a given body size are at higher risk of significant weight gain, relative to those with a high RMR. Studies in Caucasians indicate that sympathetic nervous system (SNS) activity is related to the three major components of energy expenditure: RMR, the thermic effect of food and spontaneous physical activity. Pima Indians have low SNS activity and, unlike Caucasians, their RMR does not correlate with SNS activity. A variant of the beta 3-adrenoceptor gene has been found to be weakly associated with metabolic rate. Low resting SNS activity and its apparent dissociation from metabolic rate could be a causative factor in the development of obesity.