Human recombinant interferon gamma (IFN-gamma) with a chemical purity of over 90% was shown to enhance membrane expression of HLA-DR antigens on cells from 3 human myelomonocytic lines (HL-60, U-937 and THP-1). Immunofluorescence techniques using a series of anti-HLA-DR monoclonal antibodies showed that the low, although variable, levels of DR-positive cells were clearly enhanced as soon as 24 h after incubation with IFN-gamma. Only IFN-gamma was able to exert this effect, since incubation with high concentrations of IFN-alpha or -beta did not induce any significant modification of the percentage of HLA-DR-positive cells. In contrast, doses of IFN-gamma as low as 2 units were effective, indicating a highly preferential, apparently selective effect of IFN-gamma for enhancement of HLA-DR expression. Private class II antigen expression was also enhanced by IFN-gamma on the U-937 cell line. Through its enhancing effect on class II public and private HLA antigens on the membrane of human monocytes, the IFN-gamma lymphokine may have a critical role in the modulation of antigen presentation by monocytes and on the regulation of HLA-DR-restricted cell cooperation.