The effects of 28 days of a very low calorie diet (382 Cal/day)) on the β-adrenergic lipolytic response and nutritive blood flow in sc adipose tissue were investigated in vivo using the microdialysis technique in 24 obese subjects. The diet did not modify the extracellular glycerol concentrations, but increased the local nutritive blood flow (measured by the ethanol escape method). The lipolytic response and the vasodilating effect of increasing concentrations of isoprenaline (from 0.001–10 μmol/L) added to the perfusate were enhanced after 28 days of diet. Before the diet, equimolar concentrations (100 μmol/L) of dobutamine [selectiveβ ₁-adrenoceptor (β₁-AR) agonist], terbutaline (selective β₂-AR agonist), and CGP 12,177 (selective β₃-AR agonist) increased glycerol concentration in adipose tissue. The lipolytic effect of terbutaline was the greatest, and the effect of CGP 12,177 was the least marked. After 28 days of the diet, the effects of terbutaline and CGP 12,177 were not modified, whereas the effect of dobutamine was increased and reached the effect of terbutaline. The three agonists increased nutritive blood flow; this effect was not modified during the diet. In summary, this study demonstrates an increase in the in vivo lipolytic responses to isoprenaline and dobutamine during the hypocaloric diet. Furthermore, functional β₃-AR are present in the sc adipose tissue of obese patients; however, their activation is only weakly involved in the lipolytic process in this population and is not modified by the hypocaloric diet.