It has been suggested that ankylosing spondylitis (AS) is a form of reactive arthritis similar to that observed among patients with genitourinary or intestinal infections. This hypothesis was supported by several studies which found an increased isolation rate of Klebsiella species from the stools of AS patients. The strongest known association of a human leucocyte group A antigen (HLA) with disease is observed with HLA-B27 and AS. One hypothesis proposed to explain this association is molecular mimicry, in which antigenic similarities between HLA-B27 and arthritogenic bacteria lead to a cross-reacting immune response and inflammation. Non-secretion of ABO blood group substances, an autosomal recessive characteristic, is another factor associated with susceptibility to disease, particularly to infection of mucosal surfaces. In a study in 1987, non-secretors were found to be over-represented in patients with AS, evidence which supported the hypothesis of an infectious aetiology in AS. The aims of this work were to reassess the association of non-secretion with AS; to study the faecal flora in a cohort of patients with spondylarthropathy; to determine the prevalence of bacteria expressing antigens cross-reactive with the HLA-B27 antigen; to examine the humoral responses of patients and controls to their own faecal flora; and to correlate these findings with the disease activity of the patients as assessed clinically and by the erythrocyte sedimentation rate and C-reactive protein as laboratory parameters of inflammation. The proportion of non-secretors in this AS population was identical to that in the control population when determined by haemagglutination inhibition assay and confirmed by an enzyme-linked immunosorbent assay (ELISA) for Lewis antigens. Careful scrutiny of the secretor status in a group of patients examined in both present and initial studies revealed that 27% of non-secretors in the previous survey had been wrongly typed and were indeed secretors.