Lipolysis studies were performed on isolated adipose cells obtained from two subcutaneous regions (abdominal and femoral) in 26 premenopausal women (16 obese and 10 lean subjects). Because obese adipocytes from both sites were significantly larger than lean fat cells, glycerol release measured by an ultrasensitive bioluminescent method was corrected for variation in cell surface area. Epinephrine induced antilipolysis at low concentrations and a net lipolytic response at higher doses, regardless of the subjects' fatness and the anatomic location of fat. However, the catecholamine and the selective alpha 2-adrenergic agonist, UK-14304, promoted a greater maximal antilipolytic response in both femoral and subcutaneous abdominal adipose cells from obese individuals that from lean individuals. Epinephrine- and UK-14304-induced maximal antilipolysis of femoral adipocytes was also positively associated with indicators of total adiposity. On the other hand, the maximal lipolytic responses to postadrenoceptor agents such as dibutyryl adenosine 3',5'-cyclic monophosphate, forskolin, and theophylline were lower in both adipose regions in obese than in lean women. Femoral fat cell lipolysis in the presence of these agents was negatively correlated with body fatness indexes. These results suggest that, in women covering a wide range of adiposity, variations in the lipolytic response of femoral fat cells to epinephrine may involve changes in the functional balance between alpha 2- and beta-adrenoceptors and also alterations located at different postreceptor levels.