Our own previous studies of the composition of the extracellular matrix of human failing hearts showed that collagen VI seems to play a major role in the origin of cardiac fibrosis. Therefore, collagen VI was investigated in more detail in tissue samples taken from clinically normal left ventricle and from myocardium failing because of dilated cardiomyopathy. Tissue sections prepared with collagen VI antibodies were examined by fluorescence microscopy using conventional or confocal laser scanning microscopy. In normal myocardium, collagen VI was located in both, endomysium and perimysium, in blood vessels it surrounded closely individual myocytes. Failing myocardium showed enlargement of the extracellular space and collagen VI was abundant. The localisation was perivascular as well as interstitial in fine or thick bundles enclosing the myocytes completely. In hearts with far progressed failure areas of replacement fibrosis containing increased amounts of collagen VI were evident. Double-staining for vimentin and collagen VI revealed a close interaction with fibroblasts. Although the function of collagen VI is not yet entirely clear it seems obvious that collagen VI plays an important role in the development of fibrosis in the failing heart.