Because of its role in cell adhesion, the CEACAM1 N-terminal Ig domain [22, 23, 24] , like the cytoplasmic domain, has been the focus of numerous investigations. The adhesive epitope within the N-terminal Ig-domain has been defined for rat [24] , mouse and human CEACAM1 [22, 23] , the evolutionary relationships between CEACAM1 from different species has been determined [25, 26] and the three dimensional structure has been established by X-ray crystallography [27] . In comparison, the CEACAM1 transmembrane domain has received relatively little attention, perhaps because transmembrane domains have often been viewed as passive anchor sequences that span the lipid bilayer. Over the last 10 years, this simplistic viewpoint has fallen by the wayside in the face of accumulating evidence implicating transmembrane domains in helix-helix interactions leading to dimerization, oligomerization and signal transduction [28, 29, 30] . The possible involvement of transmembrane-transmembrane domain interactions in the functionality of CEACAM1 was suggested by the presence of repeating GXXXG motifs (where X represents any amino acid), sequences known to control protein dimerization and signaling [30, 31] , and the presence of transmembrane C-terminal tyrosine residues shown in other proteins to be mediators of molecular recognition, self assembly and signal transduction [32] . In the present investigation, we have examined the effect of transmembrane domain mutations on the ability of CEACAM1-4S to confer an anchorage independent phenotype when expressed in a clonal line of CEACAM1 negative, anchorage dependent rat hepatocellular carcinoma cells, designated 253-NT. Our results show that transmembrane mutations in both GXXXG and tyrosine residues have both positive and negative effects on the anchorage independent phenotype produced by wild type CEACAM1-4S.