Tenascin (Tn) is an extracellular matrix (ECM) glycoprotein strongly and widely expressed during embryogenesis. Tn is decreased in normal adult tissues but is reexpressed in numerous inflammatory, reparative and neoplastic processes. We immunostained samples of fetal and normal adult bladders and samples of bladder tissue from patients with chronic cystitis, detrusor hypertrophy, malakoplakia and transitional cell carcinomas (TCC) of all grades, with a monoclonal antibody (mAb) to Tn 143DB7. Sections of flat in situ carcinomas were also studied. In fetal bladders, strong and ragged Tn reactions were noted at the epithelial-stromal interface; in normal adult bladders, the reaction was delicate and less extensive. In chronic cystitis, Tn reactivity was enhanced particularly around prominent capillary blood vessels. In flat in situ carcinomas, Tn staining was stronger and more extensive than in normal mucosa but was often less extensive than in some examples of cystitis. In TCC I and II, Tn immunoreactivity was strong and predominated in the pericapillary stroma of the papillae; in infiltrating TCC II, comparatively limited Tn staining was noted. In deeply infiltrating grade III TCC with abundant stroma, Tn reaction was invariably strong and extensive, particularly around advancing tumor nests. The strongest Tn reactions were noted in invasive, high-grade TCC with abundant stroma. We conclude that in inflammatory-reactive processes, and in in situ carcinomas as well as in TCC, the extent and intensity of the Tn reaction correlates with the severity of the inflammatory infiltrate and with the extent of the stromal remodelling.