Lipopolysaccharides (LPSs) from O-serotype reference strains and from serotyped isolates of Campylobacter coli were examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in combination with silver staining and immunoblotting to elucidate the molecular basis for the thermostable antigenic diversity in C. coli. Electrophoresed low-Mr LPS was detectable by silver staining and immunoblotting, but high-Mr LPS was demonstrable only by immunoblotting. Eight different antigenic specificities of low-Mr LPS were defined among the 18 serotype reference strains. In some cases, the LPSs from serotype reference strains and from field isolates of the same serotype had virtually identical low-Mr and high-Mr molecules. In other cases, the high-Mr molecules of the LPS were virtually the same for both the isolates and the corresponding serotype reference strains but low-Mr LPS of the isolate differed in both its antigenicity and it structure. The antigenic specificities of high-Mr LPS but not low-Mr LPS are the serotypic markers of the species that are identified when serotyping is performed by passive hemagglutination.