We have characterized the presence of the intercellular adhesion molecule-1 (ICAM-1) (CD54) on human intestinal adenocarcinoma cell lines as a nonreducible polypeptide of Mr 93 kDa, identified as a rhinovirus receptor. Expression of ICAM-1 was positively correlated with enterocytic maturation, in that the percentage of ICAM-1+ cells was highest in the most differentiated cell line Caco-2. ICAM-1 could be up-regulated only on the less differentiated cell lines HT29 and T84 by phorbol 12-myristate 13-acetate and by the cytokines interferon-gamma (IFN-gamma) and interleukin (IL) 1 beta. Enterocyte ICAM-1 was involved in adhesion to activated T cells through binding to the leukocyte function associated antigen-1 (LFA-1). These data provide evidence that colon adenocarcinoma cell lines express functional ICAM-1 sensitive to cytokine regulation. These findings support the hypothesis that lympho-epithelial interactions involving the ICAM-1/LFA-1 pathway may be implicated in immunosurveillance of colon adenocarcinomas, inflammatory bowel disease and celiac disease, where increased levels of proinflammatory cytokines are locally produced within the gut mucosa.