In this prospective study of childhood uveitis, 75 children with anterior uveitis were analyzed to determine whether a relationship could be found between the occurrence of uveitis, its clinical features, and humoral immunity to retinal S-antigen. For the purposes of analysis, children were divided into acute (18 cases) and chronic (57 cases) categories, depending on the duration of ocular inflammation. Clinical features of both of these groups were compared and significant differences were found in the occurrence of unilateral vs bilateral involvement, the incidence of complications, and visual outcome. Serum samples from children with acute (7 cases) and chronic uveitis (28 cases) and from healthy children (132 cases) were tested for antibodies to S-antigen by enzyme-linked immunosorbent assay (ELISA). A statistically significant difference in the level of specific antibodies between patients with chronic uveitis and controls was found. However, there was no difference between children with acute uveitis and healthy patients, nor was there any correlation between the severity of uveitis and antibody titer. For further elucidation of the significance of circulating anti-S antibodies, 14 children with chronic anterior uveitis were followed for as long as 18 months after the initial visit. Multiple serum antibody titers to bovine retinal S-antigen were determined and compared with the clinical activity at the time of each sampling. In only 6 of 14 patients did the titers to S-antigen tend to decrease with clinical improvement and stabilize at titers somewhat higher than normal values.(ABSTRACT TRUNCATED AT 250 WORDS)