The peripheral sympathetic nervous system is a key factor in the regulation of energy balance in humans. Differences in sympathetic nervous system activity may contribute to variations in 24 h energy expenditure between individuals. ß-adrenoceptors play a more important role than a-adrenoceptors in this regulation. The involvement of both ß1-and ß2-adrenoceptor subtypes has been demonstrated, the role of the ß3-adrenoceptor subtype is not yet clear. Normal or increased levels of sympathetic nervous system activity and reduced reactivity appear to be present in established obesity. Furthermore, the sensitivity for ß-adrenoceptor stimulation is impaired in obesity. The blunted reactivity and sensitivity may contribute to the maintenance of the obese state. There are data to suggest that they may also play a role in the aetiology of obesity, because the impairments often remain after weight reduction. Furthermore, a negative correlation between baseline sympathetic nervous system activity and weight gain during follow-up has been found in pima indians. Recently, genetic evidence about the involvement of adrenoceptors in obesity has become available. Although the results of association and linkage studies on polymorphisms in the ß2-, ß3- and a2-adrenoceptor genes are inconsistent, the functional correlates of some of these polymorphisms (changes in agonist-promoted down-regulation, protein expression levels, lipolytic sensitivity, basal metabolic rate, sympathetic nervous system activity) suggest that they may be important in the aetiology of obesity.