The expression of the AT1 receptor in adipose tissue is not decreased or even increased in obese subjects despite systemic activation of the renin-angiotensin system. Therefore, we hypothesized that peripheral tissues of obese subjects are hypersensitive to angiotensin (Ang) II. We characterized the effect of locally applied Ang II in skeletal muscle and subcutaneous adipose tissue of healthy non-obese (n = 12) and obese (n = 11) men using the microdialysis technique. Tissues were perfused with Ringer's solution + ethanol and incremental doses of Ang II (0.01, 0.1 and 1 micromol/l). Dialysate ethanol, glycerol, glucose, lactate, and pyruvate concentrations were measured to assess changes in blood flow (ethanol dilution technique), lipolysis and glycolysis, respectively. In adipose tissue, basal ethanol ratio was significantly higher and dialysate metabolite concentrations were significantly lower in obese versus non-obese men. In muscle, basal dialysate glycerol was significantly higher in obese versus non-obese men. Ang II elicited small increases in ethanol ratio and decreases in dialysate glucose in adipose tissue and skeletal muscle in both non-obese and obese men. Dialysate lactate increased significantly in both tissues of obese, but not non-obese men. Dialysate glycerol increased in adipose tissue of non-obese (+ 40%) but not of obese and remained almost unchanged in muscle of both groups. Interstitially applied Ang II elicits subtle changes in tissue perfusion and metabolism. However, we did not find a major increase in interstitial Ang II responsiveness in obese men.