HLA antigens are the principal serologically detectable products of the major histocompatibility complex (MHC), and they function as targets for antibody-mediated and cell-mediated cytolysis. Anti-HLA sera were used in a quantitative absorption procedure to study the effect of interferon (IF) treatment on HLA expression. This study was undertaken since IF has been shown to play an important role in the regulation of cell division and function. We found that IF enhanced the expression of HLA antigens on human peripheral blood lymphocytes by 8-fold. This increase in HLA expression was specific for both the HLA-A and HLA-B regions of the MHC. There was no increase in the expression of the Ia region after IF treatment as opposed to the HLA region. Since IF is an antiviral agent and it also enhances the expression the HLA-A and HLA-B regions, it may be involved in the elimination of virus-infected cells by A and B identical effector cells.