Adherence of the coccoid forms of Helicobacter pylori to the gastric carcinoma cell line (KATO III) was examined by transmission electron microscopy. Specialized attachment sites such as the 'adhesion pedestal', 'cup-like indentation' and 'abutting adhesion' were seen in the interaction between coccoids and epithelial cells. These adherence patterns were similar to those observed with spiral forms in gastric biopsy specimens in vivo, suggesting a possible pathogenic role for the coccoids of H. pylori. With antigens prepared from both the coccoid and spiral forms, IgG antibodies reactive to H. pylori were detected using ELISA. Patients with gastroduodenal disease accounted for 74% (37/50) ELISA positives. Of the 50 healthy blood donors, 32 and 28% were seroreactive to coccoid and spiral antigens, respectively. These sera were further characterized by Western blot where immunoreactive protein bands of 128, 116, 110, 95, 91, 66, 60, 54, 50 and 33 kD were conserved in both the coccoid and spiral forms. These findings suggest that the coccoids could be a differentiated infective form of H. pylori, and that they could evoke an immune response from the host after invading the cells via specialized attachment sites.