In the present study, footpad immunization using purified bovine retinal S-antigen mixed with complete Freund's adjuvant was used to induce experimental autoimmune uveitis (EAU) in guinea-pigs. The EAU-control group, receiving no treatment, was compared with test animals which received topically and systemically administered ethylenediamine tetra-acetic acid (EDTA) or subcutaneous and topical corticosteroid treatment, as well as a test group which received cyclosporin A subcutaneously. The severity of the uveal inflammation was clinically evaluated by slit lamp examination. The phospholipase A2 (PLA2) activity and the protein content of the aqueous humour as well as the myeloperoxidase (MPO) activity in the ciliary body were also determined. Serum antibodies to retinal S-antigen were followed using an immunoassay technique. Topical or subcutaneous EDTA significantly reduced the ocular inflammatory response to S-antigen induced autoimmune uveitis in the guinea-pigs. The best clinical suppression of EAU was obtained in the group treated subcutaneously with EDTA. Steroid treatment also suppressed the inflammatory processes in the eyes but was not as effective as EDTA or cyclosporine A. PLA2 activity in the aqueous humour and the MPO levels measured from iris-ciliary body homogenate were significantly lower in the groups treated subcutaneously with EDTA or cyclosporin A as compared with the untreated EAU-controls. The guinea-pigs treated subcutaneously with EDTA and cyclosporin A showed the lowest antiserum titres to retinal S-antigen. The prevention of PLA2 activity in aqueous humour after EDTA treatment correlated well with the milder inflammatory response in the eye. Based on the present study, it is therefore suggested that EDTA both locally and systematically reduces the S-antigen induced inflammatory response by decreasing the formation of inflammatory mediators derived from the arachidonic acid cascade.