We investigated the role of gamma/delta TCR+ T cells in induction and suppression of the T cell-mediated disease experimental autoimmune uveitis. Disease induction was studied in Lewis rats perinatally depleted of alpha/beta or gamma/delta TCR+ subpopulations. Depletion of alpha/beta TCR+ cells completely abrogated disease, whereas treatment with anti-gamma/delta antibodies had no influence on onset or intensity of uveitis. However, adoptively transferred gamma/delta+ cells from orally tolerized rats could mediate suppression of uveitis in an antigen-specific fashion. Uveitis induced by a peptide derived from the uveitogenic retinal soluble antigen (S-Ag) was suppressed by gamma/delta+ cells from rats orally tolerized with the same peptide as well as HLA peptide B27PD. This disease ameliorating effect could also be observed when rats were fed with the HLA peptide before immunization with S-Ag peptide. Transfer of alpha/beta+ T cells from the same donors as well as gamma/delta+ or alpha/beta+ cells from animals fed with control peptide had no ameliorating effect.