In the present study, we specifically investigated the presence of the main immune cells, namely T helper/inducer lymphocytes, T suppressor/cytotoxic lymphocytes, B lymphocytes and macrophages, for HLA-DR antigen expression and the cytokines IL-1 alpha and IL-2 in epiretinal membranes of proliferative diabetic retinopathy (PDR) using immunohistochemical staining. The levels of the two cytokines (IL-1 alpha and IL-2) in the vitreous were measured by ELISA. The results show that 18 out of the 32 epiretinal specimens reacted positively with monoclonal anti-CD4 (marker for T helper/inducer cell subset) antibody (56%), 21 reacted with monoclonal anti-CD8 (marker for T suppressor/cytotoxic subset) antibody (66%), 15 reacted with monoclonal anti-CD22 (marker for B lymphocytes) antibody (47%), and 25 (78%) were positive for monoclonal anti-macrophage and anti-HLA-DR antibodies. IL-1 alpha and IL-2 were detected in the epiretinal membranes in 8 out of 13 tested cases (62%). However, in the vitreous, IL-1 alpha was detected in only 3 out of 13 cases (70, 75 and 80 pg/ml, respectively), while IL-2 was not detected in any of the vitreous samples. The results clearly demonstrate that immune cells and their cytokines were found in about half of the epiretinal membrane specimens. The invasion of the immunocompetent cells in the membranes seems to be a secondary event. They would not participate in the pathogenesis of PDR, but probably induce unspecific reactions and thus complicate the disease.