Experimental autoimmune uveitis (EAU) was observed in Hartley guinea pigs following immuunization with high doses (200μg) of four synthetic peptides designated peptide 3, K. N and M which correspond to amino acid positions 221–240, 241–260. 281–302, and 303 to 320 respectively in bovine S-antigen. Histopathologically, a moderate inflammatory response involving the uveal tract and retina was observed using peptide N and peptide M as immunogens, whereas peptide 3 and peptide K. caused only a mild inflammatory response with very few inflammatory cells in the retina. In contrast, animals with EAU showed an associated pinealitis (EAP) characterized by an extensive lymphocytic infiltration of the central and subcapsular areas of the pineal gland. Lymph node cells of guinea pigs immunized with peptide 3. peptide K, peptide N or peptide M showed strongin vitroproliferative responses against the respective immunizing peptide as measured by [3H] thymidine uptake. The results suggest that under appropriate experimental conditions S-antigen may contain multiple pathogenic sites. The relevance of these studies in the pathogenesis of EAU is discussed.