The heterophilic cell adhesion mediated by CD66b (carcinoembryonic antigen (CEA) gene family member 6, CGM6) and CD66c (nonspecific cross-reacting antigen, NCA), both CEA family members expressed on neutrophils, was investigated using their soluble recombinant proteins prepared in silkworm larvae. The recombinant CD66b and CD66c immobilized on plastic bound CHO transfectants expressing CD66c and CD66b, respectively. Their deglycosylated forms retained the adhesion activity, suggesting that their carbohydrate portions are not prerequisite for the binding. This cell adhesion appeared to be mediated via interaction between the N domains of CD66b and CD66c, because CD66 antibodies recognizing their N domains inhibited the binding. Neutrophils, when activated, adhered to the immobilized CD66b and CD66c. In addition, the binding of primed neutrophils to the antigens induced superoxide anion release. The cell adhesion mediated by CD66b and CD66c may play a role in interaction between neutrophils or between neutrophils and epithelial cells expressing CD66c in vivo.