Normal human thyroid cells in monolayer culture were induced to express surface HLA class II antigens (DR and DQ) by lectin stimulation. HLA class II positive thyroid cells caused proliferation of autologous T cells, a phenomenon not found in the absence of detectable HLA class II antigen expression. Autologous T cell proliferation was further stimulated by the presence of lectin-free interleukin-2, a known stimulator of activated T cells, and inhibited by monoclonal antibody to HLA-DR antigen. These data demonstrated that normal human thyroid cells, following HLA class II antigen expression, have the capacity to stimulate the immune system. Since over 90% of the monolayer cells were thyrocytes, based on staining with antithyroid microsomal serum, and cells of the monocyte/macrophage series were absent, it is suggested that HLA class II antigen positive human thyroid cells were the principal activators of autologous T cells. Such a mechanism may be important in the target site amplification of human autoimmune thyroid disease in susceptible individuals.