Objectives. Few studies have investigated the composition of unstable coronary plaques in vivo in humans. The aims of this study were to investigate if substances released from plaques during percutaneous coronary intervention (PCI) under distal protection could give information about plaque composition and also indicate possible biomarkers in plasma that may be used to identify patients at risk. Methods and results. Twenty patients with acute coronary syndromes undergoing PCI with distal protection were included. Plasma samples were taken before, during, and after the PCI in the aortic root, locally in the culprit vessel and intravenously. Plasma was analysed for possible markers of plaque instability. During PCI, local increases were observed for matrix metalloproteinase 9 (MMP-9), protein (P <0.001) as well as activity (P < 0.001), interleukin 6 (IL-6; P < 0.01) and oxidized low-density lipoprotein (oxLDL; P = 0.01) in the culprit coronary artery. A systemic inflammatory response was also seen with increased levels of IL-10, MMP-3, serum amyloid A and C-reactive protein, but with no increase in MMP-9. Conclusions. Our study shows that local sampling of blood under distal protection may be used to analyse coronary plaques and to identify biomarkers for unstable plaques. Our results suggest that MMP-9 is a potential biomarker, and that IL-6, MMP9 and possibly oxLDL are released from plaques.