The influence of 1 week's total fasting on the lipolytic effect of adrenergic agonists and on the binding of adrenergic antagonists was examined in isolated adipocytes of subcutaneous specimens removed from the hypogastric and the femoral sites in seventeen obese women. In the femoral adipocytes the lipolytic sensitivity to isopropyl noradrenaline decreased 30-fold (P less than 0.01) during fasting. The specific binding of the radioligands (-)-[3H]-dihydroalprenolol and (-)-[125I]-cyanopindolol decreased significantly during fasting, essentially owing to a reduction in the receptor density. In adipocytes from the hypogastric region no such changes were found. For both tissue regions fasting induced a right-ward shift in the dose-response curve for the inhibitory effect of the alpha 2 agonist, clonidine, on theophylline-induced lipolysis, corresponding to a 10-fold decrease in sensitivity. There was also a significant decrease of about 20% in the alpha 2-adrenoceptor density, as estimated with the radioligand [3H]-yohimbine. The results suggest that the regulation of the lipid mobilization in man by the sympathetic nervous system during fasting occurs not only through an increase in the level of circulating noradrenaline but also through changes in the adrenergic receptor density of the adipocytes.