At sites of inflammation, cells that normally do not express class II products (la antigens) encoded by genes of the major histocompatibility complex such as fibroblasts and endothelial cells have been found to become Ia antigen positive, presumably as a result of the action of the T lymphocyte derived lymphokine gamma interferon (IFN-gamma). These cells may contribute to ongoing immunologically mediated inflammation by functioning as antigen presenting cells (APC). To test this hypothesis, fibroblasts and umbilical vein endothelial cells were treated with IFN-gamma to induce the expression of HLA-DR antigens. Both fibroblasts and endothelial cells became comparably HLA-DR positive in response to IFN-gamma. Despite this, endothelial cells but not fibroblasts became effective APC for resting T cells. HLA-DR positive fibroblasts could present antigen effectively to resting T cells; however, the HLA-DR negative endothelial cells were also present. These results indicate that expression of Ia is necessary but not sufficient for a cell to present antigen. The data also suggest that at inflammatory sites a number of cells may function in concert to promote antigen recognition by T lymphocytes.