The production of antibodies to Klebsiella capsular polysaccharides was measured in sera from either HLA-B27-positive (HLA-B27+) or HLA-B27-negative (HLA-B27-) patients with classical ankylosing spondylitis (n = 54). These sera were compared with sera from patients with various rheumatic diseases (n = 82) and HLA-B27+ or HLA-B27- healthy individuals (n = 85). All sera were analyzed by means of an enzyme-linked immunosorbent assay specific to each of the 77 Klebsiella serotypes. The sera from HLA-B27+ patients with ankylosing spondylitis showed a significantly higher antibody frequency to the capsular types K26, K36, and K50 than the sera from HLA-B27- ankylosing spondylitis patients, patients with psoriatic arthritis, systemic lupus erythematosus, rheumatoid arthritis, or reactive arthritis after Yersinia enterocolitica infection, or healthy controls (P < 0.02). The antibodies were of the immunoglobulin G type. No significant antibody response to the other 74 Klebsiella serotypes, noncapsulated mutants of K26, K36, and K50, or preparations of Citrobacter, Serratia, Hafnia, or Morganella spp. or Streptococcus pneumoniae could be detected. The results might suggest a specific association between these capsular types and HLA-B27+ ankylosing spondylitis and might imply their predominance in this disease.