AECAs have been found in 26% of patients with uveoretinitis in studies arising from three different laboratories, and their presence cannot simply be explained by coexisting extraocular disease. There is little correlation with ocular disease activity or other markers of systemic inflammation and vascular damage that can be found in this group of patients, but this lack of correlation has also been found in studies of more widespread inflammatory diseases. The changes found in the peripheral blood of patients with uveoretinitis are the result of a mixture of acute and chronic inflammation, reactions to coexisting tissue damage, as well as predisposing abnormalities of inflammation and hemostasis. Even patients with similar clinical appearances are unlikely to be pathologically homogeneous, and the reasons for the presence of AECA are likely to be various. Some patients may demonstrate a heightened antibody response to endothelium damaged by unknown mechanisms, whereas others may develop cytotoxic AECA as an integral part of the inflammatory process. The majority of serum samples with AECA demonstrated antibody-dependent cell-mediated cytotoxicity, but this potentially pathogenetic mechanism was only demonstrable in a minority of patients. It is unlikely that IgM AECA or complement-mediated cytotoxicity is a relevant mechanism of vascular damage in this group of patients. A subgroup of patients may be genetically predisposed to produce excess autoantibodies in response to tissue damage caused by a wide variety of insults. Sawyerr et al.(36) has suggested that increased serum levels of agalactosyl IgG may account for some of the AECA binding found in chronic inflammatory diseases: we have also found changes in agalactosyl IgG in patients with active isolated uveoretinitis (40), but levels did not correlate with levels of IgG AECA (unpublished results). Further longitudinal studies will be necessary on each subgroup of patients in order to determine the true clinical significance of these findings.