Cell adhesion to collagen XIV is implied to be mediated by proteoglycans as cellular receptors (T. Ehnis et al., 1996, Exp. Cell Res. 229, 388-397). In order to define the cell binding region(s), fusion proteins expressed in Escherichia coli and covering the large noncollagenous domain NC3 of collagen XIV were used as substrates for the adhesion of skin fibroblasts. A prominent cell binding site could be localized in the N-terminal fibronectin type III repeat of collagen XIV and its immediate C-terminal extension. Since this region also mediates the binding of the small chondroitin/dermatan sulfate proteoglycan decorin (T. Ehnis et al., 1997, J. Biol. Chem. 272, 20414-20419), our finding could provide the molecular basis for the observation that decorin serves as inhibitor and potential modulator of cellular interactions with collagen XIV.