In the human small intestine, proliferation, migration, differentiation and death of epithelial cells take place in separated compartments along the crypt-villus axis. It has been shown in different cell systems that these basic biological activities are influenced by extracellular matrix proteins. To investigate possible relationships in the epithelium of the human adult small intestine we examined immunohistochemically the distribution of type IV collagen, laminin, fibronectin and tenascin, and compared the sites of their expression with the various cell activities. Epithelial cell proliferation and cell death have been detected by an antibody against Ki-67 and the TUNEL-assay, respectively. The results show that Ki-67 staining is restricted to the crypts and TUNEL-positive cells are only present in the upper villus region. Type IV collagen is uniformly present in the epithelial basement membrane along the crypt-villus axis providing a scaffold for other components of the extracellular matrix. Laminin appears to be associated with epithelial cell differentiation, since it is strongly expressed in the villus basement membrane but only weakly underneath the crypt epithelium. Although fibronectin displays a staining pattern similar to that of laminin, it might rather be responsible for cell adhesion. Strong indications have been found that tenascin could be related to epithelial cell death since it was particularly expressed at the villus tip, where the cells undergo apoptosis.