The mechanisms responsible for renal cyst formation in congenital polycystic kidney disease (PKD) remain unknown. Changes in extracellular matrix (ECM) are regarded as an important pathogenic factor in PKD. Tenascin, an ECM glycoprotein implicated in abnormal growth in adult organs, has not been systematically evaluated in PKD. In this study, tenascin expression was studied by immunohistochemistry in the autosomal recessive polycystic kidneys of C57BL/6J (cpk/cpk) mice. Scanning electron microscopy was performed to determine the cyst types and their temporal evolution, and to establish correlations with the immunohistochemistry observations. Cystic lesions evolved in three main stages. Initially, the cysts appeared as segmental dilatations of both proximal and collecting ducts. In the second stage, the collecting duct cysts (CDCs) underwent rapid growth that led to the destruction of all other kidney elements. In the final stage, the CDCs reached their maximum size and the PKD mice died. Normal differentiated principal cells and three types of intercalated cells were present in the CDC epithelium. In all three stages an intense tenascin expression was detected selectively in the basement membranes of the cysts. In the last stage, an intense tenascin immunoreactivity was also observed in the interstitial fibrotic tissue. The abnormal presence of tenascin in the basement membranes of the cysts suggests that this glycoprotein is implicated in the pathogenesis of the cysts, possibly by stimulating cell proliferation.