An in vitro adherence assay was developed to study the adherence of Campylobacter pylori to mammalian cells. Strains of C. pylori were isolated from individuals with gastritis. These strains possessed the fibrillar N-acetylneuraminyllactose(neuraminlactose)-binding hemagglutinin (NLBH) and were found to adhere to monolayers of mouse Y-1 adrenal cells. Adherence was rapid, prevented by pretreatment of the Y-1 cells with Clostridium perfringens neuraminidase, and blocked by the neuraminlactose-containing protein fetuin. Electron microscopy by the immunogold technique and with anti-NLBH antibody showed that NLBH was present at the sites of interaction between C. pylori and the Y-1 cells. These results indicate that the Y-1 monolayer is a valid model for receptor-specific adherence of C. pylori.