OBJECTIVE To characterize the rheumatic diseases associated with acute anterior uveitis and examine the potential role of Yersinia enterocolitica in the pathogenesis of acute anterior uveitis. METHODS 44 patients with acute anterior uveitis were assessed for evidence of an underlying rheumatic syndrome by history and examination. HLA profiles were identified by serologic and molecular techniques. Serological analysis of patients' sera for the presence of antibodies to Y. enterocolitica was by Western blot. RESULTS 30 of the 44 patients had musculoskeletal symptoms. Of these, 8 had ankylosing spondylitis, 4 reactive arthritis, 2 undifferentiated spondyloarthropathy (SpA), 2 inflammatory bowel disease, one seronegative polyarthritis, and 13 mechanical back pain. Of 42 patients typed, 29 (69%) were HLA B27 positive and an additional 7 patients expressed a crossreactive group antigen (86% of total group B27 or CREG positive). Western blot analysis of the sera revealed increased frequency of antibodies to Yersinia compared with a control population. Antibodies directed against the 36 and 27 kDa Yersinia antigens were recognized with greater frequency (p < 0.05) in patients with acute anterior uveitis than in controls. IgG reactivity was more pronounced than IgA reactivity. Adsorption studies showed significant cross reactivity of anti-Yersinia antibodies with Salmonella typhimurium. Among the patients with acute anterior uveitis anti-Yersinia reactivity did not correlate with the HLA profile, nor with the presence of an underlying rheumatic disease. CONCLUSIONS SpA represent the commonest underlying rheumatic disorders associated with acute anterior uveitis. The majority of patients with acute anterior uveitis possess HLA-B27 regardless of whether there is underlying SpA. Patients with acute anterior uveitis show increased frequency of anti-Yersinia antibodies compared with controls. Many of these antibodies appear to be directed against antigenic determinants shared among gram negative bacteria and thus cannot constitute definitive evidence for a causal role specifically for Yersinia in acute anterior uveitis. Acute anterior uveitis represents an interplay of host susceptibility and microbial triggers, as is the case for the SpA in general.