A three dimensional structural model of the human CEACAM1 N-domain has been previously generated based on other Ig family molecules (Virji et al., 1999) . In the current investigation, we have refined our previous model based on murine CEACAM1 crystal structure (Tan et al., 2002) . Examination of this model showed a better confluence of the above residues into a continuous binding site and suggested that substitutions at positions 34 and 89 at the core of the binding region may affect bacterial access to the implicated key binding residue Ile-91. By introducing conservative and non-conservative substitutions at positions 34, 89 and 91, we have examined the binding of a variety of bacterial strains to the receptor constructs. The data suggest that single nucleotide polymorphisms (SNPs) in individuals or populations that may introduce substitutions in CEACAM sequence particularly at the bacterial binding site, could not only decrease but also significantly increase the functional affinity of pathogen interactions. Increased binding affinity may result in increased cellular invasion and thus may lead to increased host susceptibility to infection by CEACAM-targeting bacteria.