Three small peptides with a typical cysteine-rich domain (TFF or P-domain) display a specific folding structure (trefoil); they are abundantly expressed on mucosal surfaces of normal and neoplastic gastrointestinal tissues. This epithelial location coincides with mucin secretion and, although not proven beyond doubt, this association is suggestive of their function in maintenance of surface integrity. Using normal colon epithelium, premalignant lesions and tumor samples and specific antibodies we studied expression of these peptides in colorectal carcinomas. RT PCR was performed to extend the sensitivity of the assays. While coexpression of pS2, hITF, MUC1 and MUC2 was demonstrated, MUC5 was absent and no simultaneous activity of pS2 and SML1 (as in gastric mucosa and carcinoma) was noted in rectal tumors. Actively transcribed and expressed cytokeratin 20 and GAPDH were used as experimental controls for immunostaining and RT-PCR, respectively.