OBJECTIVE: Type VI collagen is a major component of the pericellular matrix compartment in articular cartilage and shows severe alterations in osteoarthritic cartilage degeneration. In this study, we analysed the exact localization of type VI collagen in its relationship to the chondrocyte and the (inter)territorial cartilage matrix. Additionally, we were interested in its ultrastructural appearance in normal and osteoarthritic cartilage. DESIGN: Distribution and molecular appearance was investigated by conventional immunostaining, by multilabeling confocal scanning microscopy, conventional transmission, and immunoelectron microscopy. RESULTS: Our analysis confirmed the pericellular concentration of type VI collagen in normal and degenerated cartilage. Type VI collagen formed an interface in between the cell surface and the type II collagen network. The type VI collagen and the type II collagen networks appeared to have a slight physical overlap in both normal and diseased cartilage. Additionally, some epitope staining was observed in the cell-associated interterritorial cartilage matrix, which did not appear to have an immediate relation to the type II collagen fibrillar network as evaluated by immunoelectron microscopy. In osteoarthritic cartilage, significant differences were found compared with normal articular cartilage: the overall dimension of the lacunar volume increased, and a significantly increased type VI collagen epitope staining was observed in the interterritorial cartilage matrix. Also, the banded isoform of type VI collagen was found around many chondrocytes. CONCLUSIONS: Our study confirms the close association of type VI collagen with both, the chondrocyte cell surface and the territorial cartilage matrix. They show severe alterations in type VI collagen distribution and appearance in osteoarthritic cartilage. Our immunohistochemical and ultrastructural data are compatible with two ways of degradation of type VI collagen in osteoarthritic cartilage: (1) the pathologically increased physiological molecular degradation leading to the complete loss of type VI collagen filaments from the pericellular chondrocyte matrix and (2) the transformation of the fine filaments to the band-like form of type VI collagen. Both might implicate a significant loss of function of the pericellular microenvironment in osteoarthritic cartilage.