Objective: Adipose tissue blood flow in humans has been rather sparsely studied, especially in response to exercise. In a recent study Stallknecht and colleagues showed evidence of increased blood flow in subcutaneous adipose tissue (SCAT) adjacent to exercising compared to resting muscle by use of xenon-washout technique (Stallknecht et al. Am J Physiol Endocrinol Metab. 292:E394-399, 2007). We investigated whether SCAT blood flow increases along with increasing exercise intensity and tested the hypothesis that adenosine plays a role in the regulation of SCAT during exercise. Methods: SCAT blood flow was measured at rest and during exercise with increasing exercise intensities using positron emission tomography (PET) and [15O]-H2O in six healthy young women. Intermittent isometric knee-extension exercise model was used (1 s contraction/2 s rest: 50, 100, and 150 N). SCAT blood flow was measured adjacent to working knee-extensors (QF) and adjacent to inactive hamstring muscles localised based on the fused images of PET and MRI. Measurements were performed without and with non- specific adenosine receptor blockade (iv theophylline). Results: SCAT blood flow adjacent to working QF increased from rest (1.0 ± 0.3 ml/100g/min) to exercise with increasing exercise intensity (4.1 ± 1.4, 5.4 ± 1.8, and 6.9 ± 3.0 ml/100g/min, p = 0.03), while blood flow in subcutaneous adipose tissue adjacent to inactive muscle remained essentially at resting level during exercise. Theophylline prevented the increase in SCAT blood flow adjacent to working QF with increasing exercise (4.3 ± 1.8, 4.0 ± 1.5, and 4.9 ± 1.8 ml/100g/min, p = 0.06), but had no effect on blood flow adjacent to inactive muscle. Conclusion: SCAT blood flow adjacent to working muscle increases with increasing exercise intensity and this increase is partly mediated by adenosine.