SIR—Uveitis associated with juvenile chronic arthritis (JCA) is the only type of uveitis that is consistently associated with a high prevalence of autoantibodies. The specificity of the antinuclear antibodies that are present include nucleosomal proteins , low-molecular-weight antigens  and histone autoantibodies . 0stensen found that antibodies to histone H3 were particularly associated with the presence of uveitis; in an earlier study, we confirmed that the prevalence of autoantibodies to five histone proteins is raised in JCA and that H3 histone antibodies were the most common . Uveitis is thought to have an autoimmune pathogenesis: strong evidence for this lies in the models of autoimmune uveitis that can be produced in experimental animals using a variety of retinal autoantigens. The most widely studied experimental uveitogen has been retinal S-antigen, a photoreceptor protein, and it has excited particular interest that there are sequence homologies between retinal S-antigen and histone H3. Histone peptides sharing sequences with the uveitogenic peptides of S-antigen can induce an identical experimental autoimmune uveoretinitis. It has been proposed that homologies between retinal antigens and widely conserved nucleoproteins may allow an immune response directed against microbial antigens to trigger autoimmune uveitis through the mechanism of molecular mimicry . Antibodies to bovine retinal S-antigen have been reported in patients with JCA-associated uveitis [6-8] and anti-photoreceptor antibodies have been found by immunofluorescence . This is unexpected, as the uveitis of JCA does not typically involve the retina where S-antigen is found. Recent ELISA studies in adult uveitis patients, using human S-antigen, have failed to demonstrate raised levels of antibodies in patients compared to controls [10, 11], even when the retina is inflamed. In a previous study, we were unable to detect any association between antibodies to histone H3 and the presence of uveitis, but antibodies to Nand C-terminal peptides were associated with the presence of uveitis. We therefore sought to confirm whether raised levels of human S-antigen antibodies occur in children with JCA-associated uveitis, and whether they correlate with the presence of antibodies to histone H3 or peptides derived from it. Standard ELISA assays were performed using retinal S-antigen prepared from human and bovine eyes. Antigen-free wells were used for controls, and normal sera from children and adults, as well as adults with uveitis were used as control populations. Raised levels were defined as sera with levels >2 S.D. from the mean of the normal adult controls. The prevalence of raised S-antigen antibody titres was as follows: adult controls, 2/24; paediatric controls, 0/7; adult uveitis, 1/12; JCA-associated uveitis, 1/69. There were no significant differences in prevalence between any of the groups; there were also no significant differences in antibody level between any of the groups (Mann-Whitney > 0.1). Antibody levels to human S-antigen correlated with antibodies to histone H2B and the antinuclear antibody titre (P < 0.05 Spearman), but did not correlate with antibodies to histone HI, H2A, H3 or H4, or the histone H3 peptides 1-25 and 130-135. Antibody titres against bovine S-antigen were similar in 46 patients and 28 controls, and again there was no difference in the prevalence of high-titre sera or the titres of antibody. The only association of antibodies to bovine S-antigen was with the total level of serum IgG. Contrary to previous reports, we could find no evidence for abnormal levels of antibodies to human or bovine retinal S-antigen in children with JCAassociated uveitis. Antibody levels did not correlate with antibodies to histone H3, and neither immunogen is likely to participate in the pathogenesis of the uveitis found in JCA. The association of antibodies to bovine S-antigen with total immunoglobulin suggests that scrupulous internal controls are required when studying these autoantibodies in subgroups of patients with increased autoantibodies and hyperglobulinaemia.