Upper-body obesity is an important risk factor for developing non-insulin dependent diabetes. To investigate the possibility that a lipolysis defect is present in this form of obesity, we examined the adrenergic regulation of lipolysis in abdominal subcutaneous fat cells from 25 women with upper-body obesity and 24 non-obese women. Lipolytic noradrenaline sensitivity (but not the maximum rate of lipolysis) was reduced by 10-fold in obese women (p<0.01). The noradrenaline resistance could be ascribed to a 10-fold decrease in lipolytic beta₂-adrenoceptor sensitivity (p<0.01). The lipolytic sensitivity of beta₁- and alpha₂-adrenergic receptors was normal in the obese women. A 70 % reduction in the cell surface density of beta₂-adrenoceptors was observed compared to the control subjects (p<0.01). However, beta₁-receptor density as well as steady-state mRNA levels for beta₁- and beta₂-receptors were normal in obese women. Lipolytic noradrenaline sensitivity correlated inversely with BMI (adjusted r ²=0.76 together with fat cell volume in stepwise regression analysis). The fasting plasma level of free cortisol was 30 % lower in obese compared to non-obese women (p<0.05) but obesity did not influence resting plasma catecholamine levels. Thus, lipolytic catecholamine resistance is present in abdominal obesity, due to low density of beta₂-adrenoceptors, which in its turn may be caused by a post-transcriptional defect in beta₂-receptor expression. Whether abnormalities in circulating free cortisol levels have caused the impaired lipolytic function of these receptors in upper-body obesity remains to be established.