Previously, we identified a unique binding site for the Fc region of IgG in goblet cells of the human small intestine and colon. Understanding of the regulation and biological role of the binding site would be enhanced if it could be studied in cultured cells. Thus, we now have searched colonic carcinoma cell lines for presence of the site and further characterized it in such cells. HT29 and HT29-18N2 (a mucin-secreting subclone) cells were capable of binding IgG. The binding was associated with mucus-producing cells only in the cultures, was enhanced by culture of the cells in galactose-containing medium (which favors mucin production) as compared to glucose-containing medium, and was much greater for the HT29-18N2 cells than for the HT29 cells. LS 174T cells did not bind IgG despite the presence of numerous mucin-containing cells, and Colo 205 and LoVo cell cultures had neither mucin-containing cells nor IgG binding; thus, IgG binding and mucin production are not inseparably linked. By use of monoclonal antibodies to three different molecular-size components of the binding site, we found that a > 200-kDa component probably is necessary but not sufficient for IgG binding, whereas 78-kDa and 110- to 140-kDa components are not necessary.