Angiotensin II is synthesized locally in various tissues. However, the role of interstitial angiotensin II in the regulation of regional metabolism and tissue perfusion has not as yet been clearly defined. We characterized the effect of interstially applied angiotensin II in abdominal subcutaneous adipose tissue of young, normal-weight, healthy men (n = 8) and women (n = 6) using the microdialysis technique. Adipose tissue was perfused with 0.01, 0.1, and 1 micro M angiotensin II. Dialysate concentrations of ethanol, glycerol, glucose, and lactate were measured to assess changes in blood flow (ethanol dilution technique), lipolysis, and glycolysis, respectively. Baseline ethanol ratio and dialysate lactate were both significantly higher, whereas dialysate glucose was significantly lower in men vs. women. In men, ethanol ratio and dialysate glucose, lactate and glycerol did not change significantly during perfusion with angiotensin II. In women, however, angiotensin II induced a significant increase in ethanol ratio and dialysate lactate and a decrease in dialysate glucose close to values found for men and this response was almost maximal at the lowest angiotensin II concentration used. Dialysate glycerol did not change significantly. We conclude that baseline blood flow and glucose supply and metabolism is significantly higher in women than in men. In men, interstitial Ang II has only a minimal effect on adipose tissue blood flow and metabolism. In women, however, a high physiological concentration of interstitial angiotensin II can reduce blood flow down to values found in men. This is associated with an impaired glucose supply and metabolism. Additionally, Ang II inhibits lipolysis.