The glycoprotein tenascin-C is up-regulated in inflammatory and neoplastic diseases. Most available data on tissue tenascin-C content do not distinguish its various isoforms. We have quantified tissue tenascin-C signals in colorectal mucosa, ulcerative colitis, colorectal carcinomas and liver metastases using 5 monoclonal antibodies (MAbs) with different binding sites. Tenascin-C of tissue extracts was analyzed by a standardized Western blot technique and densitometry. As a reference MAb, K8 displayed tenascin-C tissue concentrations of 4.1 ؎ 2.3 g/mg total protein in normal mucosa, 13.8 ؎ 4.7 g/mg in ulcerative colitis, 28.8 ؎ 14.5 g/mg in colorectal carcinomas and 25.6 ؎ 8.9 g/mg in liver metastases. The optical density values per microgram protein tissue extract of the 5 MAbs reflect the levels of the corresponding tenascin-C epitopes. Various signal intensities indicate a distinct diagnostic usefulness of the MAbs in detecting colorectal carcinomas. The binding characteristics of MAb J1/tn2 point to an under-representation of the TNfnD domain in metastasizing colorectal carcinomas, while MAb 19H12 showed an increased binding rate on the TNfnA1,2,4 region. Our comparative study of tenascin-C in inflammatory and neoplastic diseases of the colon mucosa substantiates the occurrence of large differences in the diagnostic value of tenascin-C MAbs. The detected alterations of tenascin-C in metastasizing colorectal carcinomas might indicate a prognostic value of specific tenascin-C isoforms. Int.