Using immunofluorescence and immunoperoxidase procedures, we found large amounts of IgG, IgA, IgM, and IgE, as well as C1q, C3c, and C3d, in the connective stroma and within the vascular walls on eight specimens of preretinal membranes obtained from diabetic patients with proliferative retinopathy. The membranes contained many isolated human leukocyte antigen (HLA) DR- and DQ-expressing cells, and vascular endothelial cells strongly expressed class II determinants. Monoclonal antibodies to immunocompetent cells disclosed only rare B lymphocytes or suppressor/cytotoxic T cells and few monocytes. These findings confirm previous evidence of immune reactions in the pars plana of patients with proliferative diabetic retinopathy, and suggest that an autoimmune reaction is a factor in this complication. It is yet not possible to determine whether this reaction is a nonspecific consequence of the vasoproliferative processes or if it plays a direct role in the development and extension of preretinal membranes.