Lymphocytes were obtained from the inflamed retinas of Lewis rats with S antigen (S-Ag)-induced experimental autoimmune uveoretinitis (EAU). In early disease 81% of these were CD4+ T cells. Thirty-four per cent of retinal CD4+ T cells expressed the interleukin-2 receptor (IL-2R) and 95% were CD45R-. These phenotypes contrast sharply with those of peripheral blood and lymph node CD4+ T cells isolated from EAU rats and confirm a high level of CD4+ T-cell activation in the retina in early disease. Although the relative proportions of CD8+ T cells increased in late disease, so did those of B cells and CD45R+ CD4+ T cells. We did not find clear evidence of a selective retention of CD8+ T cells in the retinas in late disease. Proliferation assays using retinal preparations demonstrated modest but significant responses to both S-Ag and the purified protein derivative of Mycobacterium tuberculosis (PPD) compared with lymph node preparations. The S-Ag response was abrogated by anti-major histocompatibility complex (MHC) class II monoclonal antibody (mAb). Lymphocyte preparations from inflamed retinas have not been examined previously in vitro but are likely to be useful in defining the precise function of CD4+ T cells during the course of EAU.