To determine whether extraintestinal isolates of Campylobacter jejuni and Campylobacter coli are the consequence of unusual host or bacterial characteristics, we studied clinical and bacteriologic features of 24 extraintestinal infections. Common serotypes and auxotypes were present among the extraintestinal isolates. Gastrointestinal isolates were more susceptible to normal human serum than were the systemic isolates; however, the ranges overlapped considerably. Predispositions to systemic spread were present in 52% of patients with extraintestinal infections; isolates from these patients were more often (73%) serum sensitive than were isolates from patients without predispositions (9%; P = .002). By sodium dodecyl sulfate-polyacrylamide gel electrophoresis, no specific protein band was associated with serum resistance, and all isolates of C. jejuni and C. coli had rough-type lipopolysaccharide profiles. Serum susceptibility was inversely correlated with carbohydrate or ketodeoxyoctonate (KDO) fraction of cell weight and directly correlated with KDO:carbohydrate ratio. Our results suggest that either host defects or specific bacterial virulence characteristics, such as serum resistance, possibly related to length of lipopolysaccharide side chain, may be responsible for extraintestinal infections due to C. jejuni and C. coli.