Tenascin-X (TNX) is an extracellular matrix glycoprotein. We previously demonstrated that TNX-null fibroblasts exhibit decreased cell-matrix and cell-cell adhesion. In this study, we used a differential display technique to determine the genes involved in this process. Differential display analysis of wild-type and TNX-null fibroblasts revealed that mRNA expression level of type VI collagen alpha3 is predominantly decreased in TNX-null fibroblasts. Expression levels of mRNAs of other subunits of type VI collagen, alpha2 and alpha3 chains, were also remarkably decreased in TNX-null fibroblasts. The protein level of alpha3 chain of type VI collagen was also reduced in TNX-null fibroblasts. However, the organization of type VI collagen in the extracellular matrix of TNX-null fibroblasts was similar to that of wild-type fibroblasts. Transient expression of TNX in Balb3T3 cells caused an increase in the level of mRNA of type VI collagen compared with that in vector control and increased the promoter activity of type VI collagen alpha1 subunit gene. In addition, the expression levels of type I collagen and other collagen fibril-associated molecules such as type XII and type XIV collagens, decorin, lumican and fibromodulin in wild-type and TNX-null fibroblasts were compared. It was found that the mRNA expression levels of type I collagen and collagen fibril-associated molecules other than decorin were decreased and that the expression level of decorin was increased in TNX-null fibroblasts. The results suggest the possibility that TNX mediates not only cell-cell and cell-matrix interactions but also fibrillogenesis via collagen fibril-associated molecules.