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A study was performed to evaluate the association of HLA‐DR antigens with the proliferative response of T cells in autologous mixed lymphocyte cultures. Peripheral blood mononuclear cells from 100 normal healthy individuals were typed for HLA‐DR antigens and autologous mixed lymphocyte cultures were established. A low proliferative response from autologous cultures was found with individuals bearing HLA‐DR3 antigens and in individuals with only one identifiable HLA‐DR antigen. In contrast, a strong proliferative response was associated with HLA‐DR6 and two identifiable HLA‐DR antigens. These data are consistent with the hypothesis that HLA‐DR3 antigens are associated with a weak immune response gene and HLA‐DR6 antigens are associated with a strong immune response gene.