This study sought to determine if coccoid forms of Helicobacter pylori are virulent for gnotobiotic piglets. Coccoid forms were generated by maintaining broth cultures of H. pylori under microaerobic conditions for 16 days. The resulting cultures contained bacteria with a coccoid morphology that could not be cultured in vitro. Coccoid H. pylori did not colonize any of 6 gnotobiotic piglets that were inoculated, whereas bacillary H. pylori colonized 6 of 6 inoculated piglets. Piglets colonized by bacillary H. pylori developed lymphocytic gastritis, but no gastritis developed in piglets inoculated with coccoid H. pylori, and coccoid-inoculated piglets were sero-negative for H. pylori-specific antibody. Thus, coccoid H. pylori appears to be a degenerate nonviable morphologic phase.